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
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
Applicant’s amendment filed May 18, 2026 is acknowledged. Claims 2-3, 6-19, 21-26, 28-30, 38-39 and 42-53 are canceled. Claims 1, 4, 5, 27, 31 and 54-57 are amended. Claims 1, 4-5, 20, 27, 31-37, 40-41 and 54-57 are pending in this application. Election was made without traverse in the reply filed on June 26, 2025.
3. Claims 1, 4-5, 20, 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.
4. Applicant’s arguments filed on May 18, 2026 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Priority
5. The priority for the claimed method recited in instant claims of the application is March 16, 2020.
The priority for the claimed method of treating relapsing multiple sclerosis (RMS) using ofatumumab in combination with an influenza vaccine in patients with RMS or patients with RMS plus with a history of at least one previous or ongoing condition other than MS was only disclosed in EP20163398.9 filed March 16, 2020 (see p.18; p. 28, claim 6 of EP20163398.9).
Response to Arguments
On p. 8-9 of the response, Applicant argues that the priority of the claimed method is Sep 11, 2019 because EP19196789.2 provides support for a method of treatment with ofatumumab and a vaccine. Applicant argues that claim 3 in EP19196789.2 supports “a method of administering ofatumumab……administration of ofatumumab is accompanied by suitable measures……alleviate adverse side effects… prophylactic measures may include vaccinations…” (see p. 19 of EP19196789.2) and claim 4 in EP19196789.2 further recites that the adverse side effects comprise “influenza”.
Applicant’s arguments have been fully considered but they are not found persuasive. Contrary to Applicant’s arguments, neither claim 3 nor claim 4 in EP19196789.2 provides support for a method of treating relapsing multiple sclerosis using a combination of ofatumumab plus an influenza vaccine because:
i. Claim 2 of EP19196789.2 only recites “a method of treating multiple sclerosis……the administration of ofatumumab is adjusted according to pre-treatment NfL levels…..”. Claim 2 does not claim a method of treating relapsing multiples sclerosis (RMS) using a combination of ofatumumab and an influenza vaccine.
ii. As admitted by Applicant, Claim 3 of EP19196789.2 only recites “The method according to claim 2 wherein the administration of ofatumumab is accompanied by suitable measures to prevent, reduce or alleviate adverse side effects….wherein the prophylactic measures may include vaccinations….during an administration period of Ofatumumab for treating Multiple Sclerosis (MS)…..” (p. 19). Claim 3 does not recite that the vaccinations include an influenza vaccine, or using an influenza vaccine together with Ofatumumab for treating RMS.
iii. As admitted by Applicant, Claim 4 of EP19196789.2 only recites “The method according to claim 2 or 3, wherein the adverse side effects comprise…….influenza”.
Claim 4 only recites adverse side effects include influenza and does not recite that an influenza vaccine or using an influenza vaccine together with Ofatumumab for treating RMS (p. 19).
iv. The claimed method of treating RMS using a combination of ofatumumab and an influenza vaccine was only disclosed in EP20163398.9 filed March 16, 2020 (see p.18; p. 28, claim 6).
Neither EP19196789.2 filed 09/11/2019 nor EP2015885.2 filed 02/21/2021 disclosed the claimed method of treating RMS using a combination of ofatumumab and an influenza vaccine because EP19196789.2 or EP2015885.2 only disclosed “ofatumumab is accompanied by suitable measures to prevent, reduce or alleviate adverse side effects….wherein the prophylactic measures may include vaccinations….during an administration period of Ofatumumab for treating Multiple Sclerosis (MS)…..” (p. 19, claim 3 of EP19196789.2; p. 37, claim 3 of EP2015885.2) or “wherein the adverse side effects comprise…….influenza” (p.20, claim 4 of EP19196789.2; p. 38, claim 4 of EP2015885.2).
Therefore, the priority for the claimed method in the instant application is March 16, 2020.
Claim Rejections/Objections Withdrawn
6. The rejection of claims 1-2, 4-9, 11, 13, 16, 18-21, 27, 31-37, 40-41 and 54-57 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, lack of scope of enablement is withdrawn in response to Applicant’s amendment to the claims and cancelation of claims
The rejection of claims 2, 6, 8-9, 11, 13, 16, 18-19 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. (J. Neurol. Sci., 1998; 159:51-53) is moot because the claims are canceled.
The rejection of claims 7 and 21 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), and further in view of Caprio et al. (J. Vasc. Med. Surg., 2016; 4:2) and Luczynski et al. (Multiple Sclerosis and Related Disorders, 2019; 27:232-238) is moot because the claims are canceled.
The provisional rejection of claims 2, 6, 8-9, 11, 13, 16, 18-19 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) is moot because the claims are canceled.
Claim Rejections/Objections Maintained
In view of the amendment filed on May 18, 2026, the following rejections are maintained.
Claim Rejections - 35 USC § 103
7. 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, 4-5, 27, 31-37, 40-41 and 54-57 stand 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) and Keyser et al. (J. Neurol. Sci., 1998; 159:51-53). The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 1, 4-5, 27, 31-37, 40-41 and 54-57 as amended are drawn to a method of treating a patient with relapsing multiple sclerosis (RMS), comprising administering to a patient in need thereof an effective amount of ofatumumab and an influenza vaccine, thereby treating RMS.
Response to Arguments
On p. 11-12 of the response, Applicant acknowledges that Leppert teaches a study plan on effects of ocrelizumab on immune responses in influenza-vaccinated MS patients. But Applicant argues that: Leppert does not provide any data from such an influenza vaccine study; ii) neither Novartis Protocoal nor Keyser cure deficiencies of Leppert; iii) Novartis Protocol is not a prior art of the instant application. Based on the PTO-892 form, the Novartis Protocol is with a date of Aug 6, 2018. But the document is not publicly available until later, on Sep 18, 2020 in view of the Record history section of the clinicaltrials.gov website posting (Exhibit A); iv) Even if Novartis Protocol were prior art, neither Novartis Protocol nor Keyser teaches vaccines in combination with Ofatumumab administration because Keyser only discusses patients with RMS vaccinated with an influenza vaccine but is silent on treatment of RMS with ofatumumab; and earlier anti-CD20 antibody therapeutics including ocrelizumab were known to be immunosuppressive and were expected to interfere with patient’s development of immunity upon vaccination.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2141, MPEP2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention obvious because:
i. The release date of NCT02792231/COMB157G2302 Clinical trial protocol is Aug 06, 2018, which predates the priority of March 16, 2020 for the claimed method. Based on the clinicaltrials.gov website, the clinical trial NCT02792231 and the method of treating RMS using Ofatumumab was publicly available on Sep 16, 2016 (see the record history of the NCT02792231 on the clinicaltrials.gov website), which predates the priority of March 16, 2020 for the claimed method. Thus, the cited reference: NCT02792231/COMB157G2302 Clinical trial protocol is prior art.
ii. In response to Applicant’s arguments related to no actual data provided by Leppert, the Examiner asserts that based on MPEP, actual data or an actual working example is not required for compliance with the enablement requirement of 35 U.S.C. 112, first paragraph.
“An example may be ‘working’ or ‘prophetic.’ A working example is based on work actually performed. A prophetic example describes an embodiment of the invention based on predicted results rather than work actually conducted or results actually achieved.”
and also In in re Borkowski, the court held that
“The specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970). See MPEP § 2164.02.
iii. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In this case, Leppert (US2018/0327505) teaches a method of treating relapsing multiple sclerosis (RMS), comprising administering to a patient in need thereof a combination of an anti-CD20 antibody including Ocrelizumab (i.e. humanized anti-CD20 monoclonal antibody) and an influenza vaccine as related to claim 1 (see para. [0555]-[0557]). Leppert teaches that the patient has a history of at least one previous or ongoing condition other than MS that is an infection caused by influenza as in claim 4, and that the influenza vaccine is administered to the patient during the anti-CD20 antibody therapy as in claim 5 or before the anti-CD20 antibody therapy as in claim 56 (see para. [0555]-[0557]), subcutaneously as in claim 27 (see para. [0130]). 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 (see para. [0115]-[0116]; [0329]-[0330]; [0446]; [0464];[0595];[0255]; [0257]-[0258]; [0265]-[0268]), 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 influenza vaccine’s prevention of influenza or does not develop influenza for at least a period of 12 months or longer after the treatment as recited in claims 54-55 (see para. [0114]).
While Leppert does not teach that the anti-CD20 antibody is Ofatumumab as recited in instant claims, at a dose of 10-30mg montly and/or subcutaneously in claim 27, or 20 mg ofatumumab 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 in claim 57, NCT02792231 and Keyser teach these limitations and provide motivation and an expectation of success because subcutaneous injection of Ofatumumab at a dose of 20mg at Days 1, 7, 14, week 4 or monthly has been used for treating relapsing multiple sclerosis (RMS) as taught by NCT02792231; and patients with RMS are more susceptible to acute respiratory infection caused by influenza virus and with a greater risk of relapse after influenza infection and illness, and that Influenza vaccination provides benefits for patients with relapsing MS to avoid serious illness such as pneumonia as taught by Keyser.
In particular, NCT02792231 (Novartis Clinical trial protocol) teaches that Ofatumumab is a fully human anti-CD20 monoclonal antibody (Ab), which is predicted to have benefits of low potential for immunogenicity and very low incidence of anti-drug antibodies against Ofatumumab (p. 21). NCT02792231 teaches a method of treating RMS, 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 Day 1 (i.e. week 0), Day 7 (i.e. week 1), Day 14 (i.e. week 2), week 4 and monthly 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 RMS are more susceptible to acute respiratory infection including infection caused by influenza virus. The patients with RMS have a greater risk of relapse after influenza infection and illness. Influenza vaccination on patients with RMS provides benefits to avoid serious illness such as pneumonia in patients with RMS (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 known benefit of influenza vaccine together with a therapeutic treatment of RMS including an anti-CD20 antibody, and the known technique disclosed by NCT02792231 and Keyser to the Leppert’s method would have yielded the predictable result of treating RMS and resulted in an improved method for treating RMS.
Using the known fully human anti-CD20 monoclonal antibody Ofatumumab in the combination of an anti-CD20 antibody and an influenza vaccine used in the Leppert’s method would treat RMS, and expand application of the Leppert’s method, and would increase patient’s satisfaction with treatment of RMS using a combination of an anti-CD20 antibody with an influenza vaccine because 1) Ofatumumab is a fully human anti-CD20 monoclonal antibody with immunogenicity and very low anti-drug antibodies against the fully human anti-CD20 monoclonal antibody, and has been used for treating RMS as taught by NCT02792231; and 2) patients with RMS are more susceptible to acute respiratory infection including infection caused by influenza virus and have a greater risk of relapse after influenza infection and illness, and a combination of the therapeutic treatment of MS including a fully human anti-CD20 monoclonal antibody Ofatumumab with an influenza vaccine provides benefits and better treatment of RMS to avoid serious illness such as pneumonia as taught by Keyer.
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 known benefit of using an influenza vaccine in combination with a therapeutic treatment of RMS including human anti-CD20 monoclonal antibody Ofatumumab for treating RMS, and the known technique disclosed by NCT02792231 and Keyser to the Leppert’s method, and yield the predictable result of better treatment of RMS and reducing relapse or avoiding serious illness such as pneumonia because patients with RMS are more susceptible to acute respiratory infection including infection caused by influenza virus and have a greater risk of relapse after influenza infection and illness, and a combination of an influenza vaccine with the therapeutic treatment of MS including a fully human anti-CD20 monoclonal antibody Ofatumumab would provide benefits and better treatment of RMS to avoid serious illness such as pneumonia.
Accordingly, the rejection of claims 1, 4-5, 27, 31-37, 40-41 and 54-57 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) and Keyser is maintained.
Claim Rejections - 35 USC § 103
8. Claim 27 stands 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, 4-5, 27, 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). The rejection is maintained for the reasons of record and the reasons set forth below.
Response to Arguments
On p. 14-15 of the response, Applicant argues that i) for the reasons set forth above, Leppert, Novartis Protocol and Keyser alone or in combination do not render claim 1 or any dependent claims obvious; ii) Kuhle and Plavina do not cure the deficiencies of Leppert, Novartis Protocol and Keyser because they focus on sNfL levels and silent on any treatment method comprising administering an anti-CD20 antibody and a vaccine.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2141, MPEP2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention obvious because:
i. For the reasons set forth above, the combined teachings of Leppert, NCT02792231 (Novartis Protocol) and Keyser do render the method of claims 1, 4-5, 27, 31-37, 40-41 and 54-57 obvious.
ii. Applicant cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In this case, while Leppert, NCT02792231 and Keyser do not explicitly teach that ofatumumab is administered when serum neurofilament light chain (sNfL) concentration is 4-13 pg/ml recited in claim 27, Kuhle and Plavina teach this limitation and provides motivation and an expectation of success because 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); and the levels of sNfL, such as 8-16 pg/ml sNf or >16 pg/ml in MS patients can be used for prediction of EDSS score or the volume of T2 lesions in patients with relapsing MS.
In particular, Kuhle teaches 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 teaches that the level of sNfL in MS patients can be used for prediction of relapsing MS based on EDSS score or the volume of T2 lesions. 12.5% of the MS patients with >16 pg/ml sNf reached an EDSS score of > 3.5 within 5 years after sNfL was measured, 7% of the MS patients with 8-16 pg/ml sNfL reached an EDSS score of ≥ 3.5 within 5 years after sNfL was measured, and only 3.3% of the MS patients with <8 pg/ml sNfL reached an EDSS score of ≥ 3.5 within 5 years after sNfL was measured. The volume of T2 lesions in MS patients with <8 pg/ml sNfL at baseline is very low, but increases in MS patients with 8-16 pg/ml sNfL at baseline and is the largest in MS patients with >16 pg/ml sNf at baseline 5 years and 10 years later (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 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); and the levels of sNfL, such as 8-16 pg/ml sNf or >16 pg/ml in MS patients can be used for prediction of EDSS score or the volume of T2 lesions in patients with relapsing MS.
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 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); and the levels of sNfL, such as 8-16 pg/ml sNf or >16 pg/ml in MS patients can be used for prediction of EDSS score or the volume of T2 lesions in patients with 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.
Accordingly, the rejection of claim 27 under 35 U.S.C. 103 as being unpatentable over Leppert et al. (US2018/0327505) in view of NCT02792231 (or COMB157G2302) and Keyser as applied to claims 1, 4-5, 27, 31-37, 40-41 and 54-57 above, and further in view of Kuhle and Plavina is maintained.
Double Patenting
9. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4-5, 20, 27, 31-37, 40-41 and 54-57 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11, 20-25, 28-32, 38, 42-44 and 47-93 of copending Application No. 17/753632, claims 64-68, 71-74, 76-102 of copending Application No. 17/995820, or claims 26-45 of copending Application No. 18/286030, claims 16-36 of copending Application No. 18/683858 or claims 1-21 and 30-32 of copending Application No. 19/526258 in view of Leppert et al. (US2018/0327505), NCT02792231 (or COMB157G2302) and Keyser et al. (1998). The rejection over Application No. 19/526258 is necessitated by an update search of inventors. The rejection is maintained for the reasons of record and the reasons set forth below.
Response to Arguments
On p. 15 of the response, Applicant argues none of the cited claims from co-pending applications recite a method comprising administering ofatumumab and an influenza vaccine.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP§ 804 and MPEP §2141, MPEP2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention obvious because:
i. While the claims of the ‘635, the ‘820, the ‘030, the ‘858 or the ‘258 Application do not recite administering an influenza vaccine together with Ofatumumab or at 20mg or specific regimens, Leppert, NCT02792231 and Keyser teach these limitations and provide motivation and an expectation of success for the reasons set forth above under the 103 rejection. 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, the ‘858 or the ‘258 Application, and yield the predictable result of better treatment of relapsing MS because Leppert teaches treating RMS using an influenza vaccine together with an anti-CD20 antibody, and subcutaneous injection of Ofatumumab at a dose of 20mg at Days 1, 7, 14, week 4 or monthly has been used for treating relapsing multiple sclerosis (RMS) as taught by NCT02792231; and patients with RMS are more susceptible to acute respiratory infection caused by influenza virus and with a greater risk of relapse after influenza infection and illness, and that Influenza vaccination provides benefits for patients with relapsing MS to avoid serious illness such as pneumonia as taught by Keyser.
Accordingly, the provisional rejection of claims 1, 4-5, 20, 27, 31-37, 40-41 and 54-57 on the ground of nonstatutory double patenting as being unpatentable over claims 1-11, 20-25, 28-32, 38, 42-44 and 47-93 of copending Application No. 17/753632, claims 64-68, 71-74, 76-102 of copending Application No. 17/995820, or claims 26-45 of copending Application No. 18/286030, claims 16-36 of copending Application No. 18/683858 or claims 1-21 and 30-32 of copending Application No. 19/526258 in view of Leppert, NCT02792231 (or COMB157G2302) and Keyser is maintained.
New Grounds of Rejection Necessitated by the Amendment
The following rejections are new grounds of rejections necessitated by the amendment filed on May 18, 2026.
Claim Rejections - 35 USC § 103
10. Claim 20 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 et al. (1998) as applied to claims 1, 4-5, 27, 31-37, 40-41 and 54-57 above, and further in view of Vaugh et al. (Nat. Rev. Neurol. 2019; 15:329-342, abstract) and Otallah et al. (Curr. Neurol. Neurosci. Rep. 2018; 18:76. Doi.org/10.1007/s11910-018-0886-7).
Leppert, Novartis Protocol and Keyser are set forth above but do not teach
that the patient is a geriatric patient or a pediatric patient as in claim 20.
Vaugh et al. teaches ageing individuals with multiple sclerosis (MS) is increasing and currently approved therapies for MS are effective in preventing relapse of MS (see abstract).
Otallah et al. teach pediatric-onset multiple sclerosis (POMS) shares the degenerative aspects that also characterize adult-onset disease and can be treated with anti-CD20 monoclonal antibody that has been approved for adult MS or RMS (see abstract; p.5, 2nd col. last para.to p.6, 1st col., 1st para).
A person of ordinary skill in the art would have recognized that selecting and applying the known geriatric patients or pediatric patients with RMS and the known technique disclosed by Vaugh and Otallah to the method of Leppert, NCT02792231 and Keyser would have yielded the predictable result of treating relapsing MS in geriatric patients or pediatric patients and resulted in an improved method.
Including and treating geriatric patients or pediatric patients with RMS in the method of Leppert, NCT02792231 and Keyser would treat relapsing MS in geriatric patients or pediatric patients with RMS, 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 geriatric patients or pediatric patients also share the degenerative aspects that also characterize adult-onset disease and can be treated with anti-CD20 monoclonal antibody that has been approved for adult MS or RMS as taught by Vaugh and Otallah.
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 geriatric patients or pediatric patients with RMS and the known technique disclosed by Vaugh and Otallah to the method of Leppert, NCT02792231 and Keyser, and yield the predictable result of treating relapsing MS.
Conclusion
11. NO CLAIM IS ALLOWED.
12. 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).
13. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
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, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Chang-Yu Wang
July 28, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
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