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 of Group I (claims 64-101), ocrelizumab in the reply filed on November 24, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Upon reconsideration, the species election between rituximab and Ocrelizumab is withdrawn. The subject matter to the extent of rituximab is included and under examination in this office action.
Claims 1-63 are canceled. Claims 64-101 are pending in this application and under examination in this office action.
Priority
5. 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, EP20169007.0 filed April 09, 2020 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 multiple sclerosis (MS), comprising administering ofatumumab to a patient who has exhibited a decrease in serum IgG level including below a concentration of 900mg/dL, 800mg/dL or 700mg/dL after receiving an earlier disease-modifying therapy other than ofatumumab or the serum IgG level is below 80% of the baseline level at the start of the earlier-disease-modifying therapy including an immunosuppressive therapy other than ofatumumab, which is not presented in EP20169007.0 filed April 09, 2020. The claimed method of treating MS comprising administering ofatumumab to a patient who has exhibited a decrease in a serum IgG level after receiving an earlier-modifying therapy other than ofatumumab was only disclosed in EP20176057.6 filed on May 22, 2020. Therefore, the priority for the claimed method in the instant application is May 22, 2020.
Information Disclosure Statement
6. 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
7. The disclosure is objected to because of the following informalities: The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (p. 26). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Appropriate correction is required.
Claim Rejections - 35 USC § 112
8. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 64 and 69-101 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 64 and 69-101 are indefinite because:
i. The term "a decrease in a serum IgG level…” in claim 64 or the term “increases the serum IgG level” in claim 73 is a relative term which renders the claim indefinite. The term "a decrease in a serum IgG level…" or “increases the serum IgG level” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Applicant fails to set forth the metes and bounds of what is encompassed within the definition of “a decrease in a serum IgG level…” or “increases the serum IgG level”. Since the metes and bounds are unknown, a skilled artisan cannot envision what would be considered as “a decrease in a serum IgG level…” or “increases the serum IgG level” recited in the claim. Thus the claim is indefinite.
ii. The rest of claims are indefinite as depending from an indefinite claim.
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 64-101 are rejected under 35 U.S.C. 103 as being unpatentable over Novartis-NCT02792231 (or COMB157G2302, Novartis Clinical trial protocol, published Aug 06, 2018) in view of Zoehner et al. (Ther. Adv. Neurol. Disord., 2019; 12:1-8. Doi:10.1177/17562864198878340), Hallberg et al. (Oral Presentations, Number 64: Risk of hypogammaglobulinemia in long-term treatment with rituximab in multiple sclerosis, p. 20; Multiple Sclerosis J. 2019; 25: (S2) 3-130), Derfuss et al. (Oral Presentations, Number 65: Serum Immunoglobulin levels and risk of serious infection in the pivotal phase III trials of ocrelizumab in multiple sclerosis and their open-label extensions, p. 20; Multiple Sclerosis J. 2019; 25: (S2) 3-130) and Bar-Or et al. (Poster Number p6.1-008, the 72nd Annual Meeting of the American Academy of Neurology, April25-May 01, 2020; Toronto, ON, Canada).
Claims 64-101 as amended are drawn to a method of treating multiple sclerosis (MS), comprising administering ofatumumab to a patient who has exhibited a decrease in serum IgG level after receiving an earlier disease-modifying therapy other than ofatumumab.
Novartis-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 multiple sclerosis (MS) including relapsing MS, 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 recited claims 95-97 (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). Novartis-NCT02792231 also teaches that the ofatumumab is formulated in an amount of about 20-300mg/ml or 50mg/ml as in claims 98-99 (see p. 37; p.21), wherein the multiples sclerosis is relapsing multiple sclerosis (RMS), primary progressive multiple sclerosis (PPMS) or progressive relapsing multiple sclerosis (PRMS) (claims 100-101) .
But Novartis-NCT02792231 does not teach that the patient has exhibited a decrease in serum IgG level including below a concentration of 900mg/dL, 800mg/dL, below a lower limit of normal (LLN) of 700mg/dL or below 80% of the baseline after receiving an earlier disease-modifying therapy other than ofatumumab recited in claim 64-67, below 80% of the baseline level at the start of the earlier disease-modifying therapy in claim 68,or an immunosuppressive therapy other than ofatumumab, including anti-CD20 antibody, rituximab or ocrelizumab for the disease-modifying therapy as recited in claims 69-71, ofatumumab is administered for at least 96 weeks as in claim 72, administration of ofatumumab maintains or increases the serum IgG level of the patient at no less than 50% of a LLN of 700mg/dL, above LLN of 700 mg/dL, 800mg/dL, 900mg/dL or increases about 3% as compared to before administration of Ofatumumab as in claims 73-94.
Zoehner et al. teach that the lower limits of normal (LLN) for serum IgG is <700mg/dL and the serum IgG concentrations in MS patients were frequently under LLN, and below 600mg/dL compared with control patients (see abstract; p 3, 1st col., 2nd paragraph). Zoehner teaches that secondary progressive MS (SPMS) patients had lower IgG concentrations than relapsing–remitting (RRMS) and primary progressive patients (PPMS) because SPMS patients had a concentration of 690–850mg/dL (average=750mg/dL), RRMS patients had a concentration of 800–1110 mg/dL (average= 950mg/dL) PPMS patients had a concentration of 830-1120mg/dL (average=940mg/dL) (p. 3, 2nd col.). Zoehner teaches that the IgG concentrations were lower in patients treated with rituximab, intravenous corticosteroids, natalizumab and fingolimod (i.e. immunosuppressive therapy) as compared to . Zoehner teaches that when IgG levels are much lower, at or below 400mg/dl, infections or interference with antibody production generally occur and the information is useful to monitor IgG levels especially with anti-B-cell therapies and consider IgG substitution when levels drop below 400mg/dl (see abstract). The concentration of 750mg/dL disclosed by Zoehner is below a concentration of 900mg/dL or 800mg/dL recited in claims 65-66, 77-78 and 84-85 and 91-92. The concentration of 600mg/dL or 400mg/dL disclosed by Zoehner is below a LLN of 700mg/dL or no less than 50% of a LLN of 700mg/dL recited in claims 67-68, 75-76, 82-83, 89-90
Hallberg et al. teach that MS patients treated with rituximab developed serum IgG levels below 6.7g/L (670mg/dL) and had a decrease in serum IgG levels of 2g/L (200mg/dL) (abstract). The concentration of 670mg/dL and a decrease of 200mg/dL disclosed by Hallberg is below a LLN of 700mg/dL recited in claims 67-68, 75-76,82-83 and 89-90.
Derfuss et al. teach that MS patients treated with ocrelizumab (OCR) resulted in reduction in the serum IgG levels. Derfuss teaches that the lower limit of normal (LLN) is defined as 565mg/dL and the reduction in serum IgG levels from baseline to 264 weeks in RMS treated with is 17% (from 1053mg/dL to 879mg/dL), the reduction in PPMS treated with OcR is 16.9% (from 1068mg/dL to 896 mg/dL), and a reduction in serum Ig levels is highly associated with increased rates of serious infection (see abstract). The concentration 879mg/dL or 896 mg/dL is below 900mg/dL recited in claims 66, 78, 85 and 92.
Bar-Or et al. teach MS patients treated with ocrelizumab (OCR) resulted in reduction in the serum IgG levels and the rate of reduction is ~3% from the baseline (see p. 11, Figures).
A person of ordinary skill in the art would have recognized that selecting and applying the known results of reduction in the serum IgG levels in MS patients after being treated with an earlier disease-modifying therapy such as anti-CD20 antibody including rituximab or ocrelizumab and the known decreased serum IgG levels of below 900mg/dL, 800mg/dL, below a LLN of 700mg/dL, no more than 50% of a LLN of 700mg/dL, or below 80% of the baseline or with a reduction rate of about 3% after receiving an earlier disease-modifying therapy such as anti-CD20 antibody including rituximab or ocrelizumab and the known technique disclosed by Zoehner, Hallberg, Derfuss and Bar-Or to the method of Novartis-NCT02792231 would have yielded the predictable result of treating MS including RMS, PPMS and PRMS, and resulted in an improved method for treating MS.
Using the known reduction in the serum IgG levels in MS patients after being treated with an earlier disease-modifying therapy such as anti-CD20 antibody including rituximab or ocrelizumab and the known decreased serum IgG levels of below a LLN of 700mg/dL, no more than 50% of a LLN of 700mg/dL, below 900mg/dL, below 800mg/dL, below 80% of the baseline or with a reduction rate of about 3% after treatment with rituximab or ocrelizumab in the method of Novartis-NCT02792231 would maintain the serum IgG level of the MS patient above a concentration of a LLN of 700mg/dL, at no more than 50% of a LLN of 700mg/dL, 800mg/dL or 900mg/dL or increase the serum IgG levels by about 3% compared to before administration of Ofatumumab because treatment of rituximab or ocrelizumab in MS patients results in reduction in the serum IgG levels of below a LLN of 700mg/dL, at no more than 50% of a LLN of 700mg/dL, below 800mg/dL or below 900mg/dL, and discontinuation of the treatment with rituximab or ocrelizumab in MS patients and switching the treatment to Ofatumumab would stop further reduction in the serum IgG levels in MS patients, and would maintain or increase the serum IgG levels at a LLN of 700mg/dL, at no more than 50% of a LLN of 700mg/dL, 800mg/dL or 900mg/dL or increase the serum IgG levels by about 3% as compared to before administration of Ofatumumab, and would expand application of the method of Novartis-NCT02792231, and would increase patients’ satisfaction with treatment using an anti-CD30 antibody including Ofatumumab.
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 reduction in the serum IgG levels in MS patients after being treated with an earlier disease-modifying therapy such as anti-CD20 antibody including rituximab or ocrelizumab and the known decreased serum IgG levels of below a LLN of 700mg/dL, no more than 50% of a LLN of 700mg/dL, below 900mg/dL, below 800mg/dL, below 80% of the baseline or with a reduction rate of about 3% after treatment with rituximab or ocrelizumab and the known technique disclosed by Zoehner, Hallberg, Derfuss and Bar-Or to the method of Novartis-NCT02792231 and yield the predictable result of treating MS and stopping further reduction in the serum IgG levels in MS patients caused by rituximab or ocrelizumab to maintain or increase the serum IgG levels of the patient at above a LLN of 700mg/dL, at no more than 50% of a LLN of 700mg/dL, above 800mg/dL or above 900mg/dL or increase the serum IgG levels by about 3% as compared to before administration of Ofatumumab.
Double Patenting
11. 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 64-101 are 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 1, 2, 4-7, 9, 18-21, 27, 31-37, 40-41 and 54-57 of copending Application No. 17/753,635, claims 26-45 of copending Application No. 18/286,030, or claims 16-36 copending Application No.18/683858 in view of Novartis-NCT02792231 (2018), Zoehner et al. (2019), Hallberg et al. (2019), Derfuss et al. (2019) and Bar-Or et al. (2020).
Claims 1-11, 20-25, 28-32, 38, 42-44 and 47-93 of Application No. 17/753632 (the ‘632 Application) claim a method of treating relapsing multiple sclerosis, comprising administering ofatumumab to a patient who has been treated with a disease-modifying therapy other than ofatumumab, wherein the disease-modifying therapy includes anti-CD20 therapy including ocrelizumab or rituximab (claims 70-75).
Claims 1, 2, 4-7, 9, 18-21, 27, 31-37, 40-41 and 54-57 of Application No. 17/753635 (the ‘635 Application) claim a method of treating relapsing multiple sclerosis (RMS), comprising administering ofatumumab to a patient in need thereof an effective amount of ofatumumab and a vaccine, thereby treating or preventing RMS, and wherein the patient is treated with an immunosuppressive agent other than Ofatumumab including an antibody, rituximab (claims 9, 13, 18-19).
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 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.
Claims 16-36 of Application No. 18/683,858 (the ‘858 Application) claim a method of treating multiple sclerosis (MS), comprising administering ofatumumab to a patient who has at most 40kg body weight and/or aged between 5 and <18 years, wherein the patient includes a patient who has received an MS disease-modifying therapy other than ofatumumab including anti-CD20 therapy including ocrelizumab or rituximab (claim 26-27).
While the claims of the ‘632 Application, the ‘635 Application, the ‘030 Application and the ‘858 Application do not explicitly recite that the patient has exhibited a decrease in serum IgG level including below a concentration of 900mg/dL, 800mg/dL, below a lower limit of normal (LLN) of 700mg/dL or below 80% of the baseline after receiving an earlier disease-modifying therapy other than ofatumumab recited in claim 64-67, below 80% of the baseline level at the start of the earlier disease-modifying therapy in claim 68,or an immunosuppressive therapy other than ofatumumab, including anti-CD20 antibody, rituximab or ocrelizumab for the disease-modifying therapy as recited in claims 69-71, ofatumumab is administered for at least 96 weeks as in claim 72, administration of ofatumumab maintains or increases the serum IgG level of the patient at no less than 50% of a LLN of 700mg/dL, above LLN of 700 mg/dL, 800mg/dL, 900mg/dL or increases about 3% as compared to before administration of Ofatumumab as in claims 73-94, Novartis-NCT02792231, Zoehner, Hallberg, Derfuss and Bar-Or teach these limitations and provide motivation and an expectation of success for the reasons set forth above.
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 reduction in the serum IgG levels in MS patients after being treated with an earlier disease-modifying therapy such as anti-CD20 antibody including rituximab or ocrelizumab and the known decreased serum IgG levels of below a LLN of 700mg/dL, no more than 50% of a LLN of 700mg/dL, below 900mg/dL, below 800mg/dL, below 80% of the baseline or with a reduction rate of about 3% after treatment with rituximab or ocrelizumab and the known technique disclosed by Novartis-NCT02792231, Zoehner, Hallberg, Derfuss and Bar-Or to the method of the ‘632 Application, the ‘635 Application, the ‘030 Application and the ‘858 Application and yield the predictable result of treating MS and stopping further reduction in the serum IgG levels in MS patients caused by an earlier disease-modifying therapy including anti-CD20 antibody such as rituximab or ocrelizumab to maintain or increase the serum IgG levels of the patient at above a LLN of 700mg/dL, at no more than 50% of a LLN of 700mg/dL, above 800mg/dL or above 900mg/dL or increase the serum IgG levels by about 3% as compared to before administration of Ofatumumab.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
12. NO CLAIM IS ALLOWED.
13. 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 on Monday-Thursday, 7:00am-5:00pm EST.
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Chang-Yu Wang
January 10, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675