DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment filed on June 17, 2026 is acknowledged.
Claims 2, 4, 6, 12, 14-16, 19-30, 32-38, 40-45, 47-52, 54-61, 63-69, and 71-75 have been canceled.
Claims 1, 3, 5, 7-11, 13, 17, 18, 31, 39, 46, 53, 62, and 70 are pending and currently under consideration.
3. In view of applicant’s amendment, following rejections are set forth.
4. 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.
5. Claims 1, 3, 7-11, 13, 17, 18, 31, 39, 46, and 70 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The claims are indefinite in the recitation of “wherein the patient had been previously treated with an anti-CD20 antibody, wherein the anti-CD20 antibody is rituximab, wherein the subject had an NMOSD attack while being treated with or within 6 months of the last dose of the anti-CD20 antibody” in independent claims 1 and 39 because the metes and bounds of the phrase is unclear. The meaning of “wherein the subject had an NMOSD attack while being treated with” the anti-CD20 antibody.
The specification discloses that seven of 17 patients entered study as rituximab “failures” defined as having an NMOSD attack while on of the last dose of rituximab (e.g. see [0135]).
It was known in the art that there were several Rituximab treatment regiments for NMOSD treatment. For example, Damato et al. (JAMA Neurology 2016 73;11:1342-1348, E1-E7) teach Rituximab regimen including weekly for 4 weeks, every two weeks twice, weekly for two weeks, or other regiments (e.g. see Table in page E3). It is not clear what defines as “attack while being treated with the anti-CD20 antibody”. Does it mean attacks occurred before the end of regimen or during the regimen? A patient could be already finishing administration of Rituximab and still be considered being treated with Rituximab.
As such, the claims fail to particularly point out and distinctly claim the subject matter. For the purpose of examination and application of prior art, the limitation is read as any patient previously being treated with Rituximab.
6. 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 (i.e., changing from AIA to pre-AIA ) 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.
7. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
8. Claims 1, 3, 7-11, 13, 17, 18, 31, 39, 46, and 70 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cree et al. (Lancet 2019; 394:1352-63, published online September 5, 2019).
The instant claims recite anti-CD19 antibody CDRs sequences and VH and VL amino acid sequences. As evidenced by the instant specification, the recited sequences are the CDRs, VH, and VL of anti-CVD19 antibody VIB551 (e.g. see Figures 4 and 9 and page 10 of the specification as filed). As further evidenced by [0038] the instant specification as filed, inebilizumab is VIB551.
Further, the limitation of “wherein the patient had been previously treated with anti-CD20 antibody, wherein the anti-CD20 antibody is rituximab, wherein the subject had an NMOSD attach while being treated with” the last dose of the anti-CD20 antibody is interpretated as being previously treated with rituximab and also had NMOSD attack (see detailed discussion above).
Creed et al. teach NMOSD is predominantly a B cell-mediated disorder resulting from pathological autoantibody production, pro-inflammatory cytokine secretion, and B-cell antigen presentation (e.g. see right col. in page 1352). Immunosuppresants such as corticosteroids and B cell-depleting drug rituximab are used to prevent attacks (e.g. see right col. in page 1352).
Creed et al. teach evidence suggests a clinical benefit for anti-CD20 antibody rituximab which deplete CD20-expressing T lymphocytes in addition to B lymphocytes, while anti-CD19 antibodies recognize and deplete a wider range of lymphocytes exclusively from the B-cell lineage (e.g. see lower cols in page 1353).
Cree et al. teach treatment of neuromylitis optica spectrum disorder (NMOSD) by administering 300 mg anti-CD19 antibody inebilizumab intravenously on days 1 and 15 (e.g., see Methods in page 1352). Cree et al. further teach that one group of the patients is AQP4-IgG seropositive and also previously been treated with anti-CD20 antibody rituximab (e.g. see Table 1 in page 1356). The patients to be treated must meet criteria including an Expanded Disability Status Scale (EDSS) score of 8.0 or less, a history of either at least one attack requiring rescue therapy during the year before screening or at least two attacks requiring rescue therapy in the 2 years before screening, indicating the patient group previously been treated with rituximab would also have at least one attack during the year before screening or two attacks in the two years before screening (e.g. see Participants in left col. in page 1353).
Cree et al. further teach all patients received oral corticosteroids between days 1 and 14 in addition to inebilizumab (e.g. see right col. in page 1353).
Cree et al. teach that compared with placebo, inebilizumab reduced the risk of an NMOSD attack (e.g. see page 1352). Fewer participants had EDSS score worsening from baseline and MRI lesion counts were lower in the inebilizumab group (e.g. see paragraph spanning pages 1357-1358).
Therefore, the reference teachings anticipate the instant invention.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues that the claims have been amended to add “wherein the anti-CD20 antibody is rituximab, wherein the subject had an NMOSD attach while being treated with or whining 6 months of the last dose of the anti-CD20 antibody” which is not disclosed in Cree et al. As such, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
Contrary to applicant’s reliance on the newly added limitations, note that the claims still recite wherein the patient had been previously treated with rituximab. Further, given that the meaning of “wherein the subject had an NMOSD attach while being treated with the last dose of the anti-CD20 antibody” is vague and ambiguous (see detail analysis above), the claims are read as treating patients previously treated with rituximab.
Here, Cree et al. teach treating NMOSD human patients with the anti-CD19 antibody wherein the patients had previously treated with rituximab and had attack or relapses one year before the anti-CD19 antibody treatment. As such, the reference teachings anticipate the instant invention. Applicant’s arguments have not been found persuasive.
9. 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, 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.
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.
10. Claims 1, 3, 5, 7-11, 13, 17, 18, 31, 39, 46, 53, 60, and 70 are rejected under 35 U.S.C. 103 as being unpatentable over by Cree et al. (Lancet 2019; 394:1352-63, published online September 5, 2019) and Katz et al. (WO 2020/219743, reference on IDS) in view of Damato et al. (JAMA Neurology 2016 73;11:1342-1348, E1-E7).
The instant claims recite anti-CD19 antibody CDRs sequences and VH and VL amino acid sequences. As evidenced by the instant specification, the recited sequences are the CDRs, VH, and VL of anti-CVD19 antibody VIB551 (e.g. see Figures 4 and 9 and page 10 of the specification as filed). As further evidenced by [0038] the instant specification as filed, inebilizumab is VIB551.
The teachings of Cree et al. have been discussed above.
Similarly, Katz et al. teach a method of treating NMOSD by administering an anti-CD19 antibody VIB551, a humanized, affinity-optimized afucosylated IgG1 antibody (e.g. see Abstract). Katz et al. teach that administering the VIB551 to a NMOSD patient at a dosage of 300 mg every 6 month (e.g. see claim 1). Katz et al. also teach a method of reducing disability severity scale (e.g. see claim 2), a method of reducing number of MRI lesions (claim 4), a method of reducing NMOSD-related attack of the patient (claim 9).
Katz et al. teach that the patient is AQP4-IgG seropositive (claim 26). Katz et al. further teach clinical trial includes patients had been previously treated with anti-CD20 antibody rituximab (e.g. see Table 9 in page 55). Katz et al. teach method of reducing disability, reducing active MRI lesions, reducing NMOSD-related attacks in NMOSD patients (e.g. see [0008]-[0012]).
Katz et al. teach the patients to be selected for treatment must meet criteria including positive anti-AQP4-IgG, one or more acute relapse that required therapy within last year or two or more acute relapses that required rescue therapy within 2 years prior to screening (e.g. see [0117]).
Katz et al. further teach that treating NMOSD patients with VIB551 can reduce the worsening of the EDSS, reducing pain, reducing hospitalization (e.g. see [0033]). Katz et al. teach the initial dose of 300 mg VIB551 can be followed by another administration in two weeks (e.g. see [0065] and Table 2 in page 38).
The reference teachings differ from the instant invention by not describing the subject had been previously treated with an anti-CD20 antibody, and had an NMOSD attack while being treated with or within 6 months of the last dose of the anti-CD20 antibody.
Both Cree et al. and Katz et al. teach treating NMOSD human patients by administering the anti-CD19 antibody VIB 551 to patients previously treated with anti-CD20 antibody Rituximab and wherein the patients must meet criteria including an Expanded Disability Status Scale (EDSS) score of 8.0 or less, a history of either at least one attack requiring rescue therapy during the year before screening or at least two attacks requiring rescue therapy in the 2 years before screening.
Damato et al. teach Rituximab has been increasingly adopted as a first-line off-label treatment for patients with NMOSDs (e.g. see page E1). Damato et al. teach that while Rituximab may reduce the frequence of NMOSD relapses and neurological disability, the safety profile suggest caution (e.g. see Key Points in E2).
Damato et al. teach Rituximab primarily acts by depleting plasma cell precursors, namely late pre-B cell stage and it has been demonstrated that rituximab therapy does not alter the frequencies of autoreactive and polyreactive B cells, therefore, does not reset the defective early B-cell tolerance checkpoints. This finding can explain the occurrence of NMOSD relapses after rituximab therapy in some NMOSD patients (e.g. see left col. in page E5).
In contrast to Rituximab, anti-CD19 antibody VIB551 was known to anti-CD19 antibodies recognize and deplete a wider range of lymphocytes exclusively from the B-cell lineage (see discussion of Cree et al. above).
It would thus be obvious to one of ordinary skill in the art at the time the instant invention was made to treat NMOSD patients who were previously treated with Rituximab but still have NMOSD relapses with the anti-CD19 antibody VIB551. Given that it was known in the art that Rituximab primarily depletes late pre-B cell and there is occurrence of NMOSD relapses after rituximab therapy as disclosed in Damato et al. and in view of the teachings of Cree et al. and Katz et al. that anti-CD19 antibody VIB551 is effective in treating NMOSD patients previously treated with Rituximab but still experience at least one attack, an ordinary skill in the art would have been motivated to treat NMOSD patients previously treated with Rituximab with unsatisfied results with a reasonable expectation of success.
Further, it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was filed to determine all operable and optimal intervals of treatment, e.g. while being treated with Rituximab but not achieving optimal outcomes or within six months of the last dose of Rituximab. Because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Further, if there are any differences between Applicant’s claimed method and that suggested by the teachings of the prior art, the differences would be appear minor in nature.
Although the prior art references do not teach all the various permutations of interval ranges such as administering intravenously a second dose of 300 mg two weeks after the first initial dose of 300 mg VIB551, it would be conventional and within the skill of the art to identify the optional intervals of treatment . Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP §§ 2144.05 part II A.
11. No claim is allowed.
12. 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.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHUN W DAHLE/Primary Examiner, Art Unit 1641
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