DETAILED ACTION
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 .
Election/Restrictions
Applicant’s election of a multispecific antibody comprising an anti-BCMA antibody or antigen-binding fragment comprising heavy chain CDR 1, 2, and 3 of SEQ ID NO: 21, 22, and 17 with light chain CDR 1, 2, and 3 of SEQ ID NO: 27, 28, and 20 and anti-CD3 antibody or an antigen-binding fragment comprising a heavy chain CDR 1, 2, and 3 of SEQ ID NO: 1, 2, and 3 with light chain CDR 1, 2, and 3 of SEQ ID NO: 4, 5, and 6. in the reply filed on 29 December 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)).
Claims 11 and 40-45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/29/2025.
Applicant’s election of myasthenia gravis in the reply filed on 29 December 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)).
The genus of autoimmune diseases are rejoined by the examiner.
Claim Status
Claims 14-17, 19, 23, 25-28, 30-33, and 36 are cancelled. Claims 1-13, 18, 20-22, 24, 29, 34-35, and 37-45 as filed on 29 December 2025 are pending. Claims 11 and 40-45 are withdrawn. Claims 1-10, 12-13, 18, 20-22, 24, 29, 34-35, and 37-39 are under examination.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 4-5, 12, 18, 24, and 39 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vu (WO 2014122144 A1) (IDS), as evidenced by Grammatikos & Tsokos. Trends in Molecular Medicine. 18(2):101-108. (2012) (PTO-892).
Regarding claims 1-2, 4-5, 12, and 39, Vu teaches bispecific antibodies that bind BCMA and CD3 for use in treatment of autoimmune diseases including systemic lupus erythematosus (SLE) (Examples 3 and 10).
Regarding claim 18, the claim is to a method of treating an autoimmune disorder that is refractory or relapsed and/or newly diagnosed. By teaching the treatment of autoimmune disease this would inherently include the patient population of the claims.
Regarding claim 24, Vu teaches the treatment of SLE which has an inherent increased risk of infection as evidenced by Grammatikos & Tsokos (Abstract and page 102 in col 1 in par 1-2).
Claims 1-2, 4-10, 12, 24, 29, 34, and 37-39 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vu 2017 (WO 2017021450 A1 ) (IDS).
The anti-BCMA antibody comprising instant SEQ ID NO: 10 and 14 comprises the HCDRs of SEQ ID NO: 21, 22, and 17 with LCDRs of SEQ ID NO: 27, 28, and 20 is Mab42. Instant SEQ ID NO: 10 matches SEQ ID NO: 10 of Vu 2017 and instant SEQ ID NO: 14 matches SEQ ID NO: 14 of Vu 2017.
The anti-CD3 of the claims comprises instant SEQ ID NO: 7 and 8. Instant SEQ ID NO: 7 matches SEQ ID NO: 7 of Vu and instant SEQ ID NO: 8 matches SEQ ID NO: 8 of Vu.
By teaching the instant SEQ ID NO: 7-8, 10, and 14 Vu teaches the sequences of the CDRs and VH and VL of claims 7-10.
Regarding claims 1-2, 4-5, 7-8, 12, and 39, Vu 2017 teaches bispecific antibodies that bind BCMA and CD3 comprising Mab42 (page 30 in lines 12-21). Vu 2017 teaches a pharmaceutical composition comprising the antibodies of its invention for treating the autoimmune disease SLE (page 18 in lines 28-29 and claim 43).
Regarding claim 6, Vu 2017 teaches the bispecific in the structure of BCMA Fab - Fc – CD3 Fab – BCMA Fab in Figures 2A and 2B and page 9 under bullet 25.
Regarding claim 24, Vu 2017 teaches testing for cytokine release syndrome with administration of the anti-BCMA/anti-CD3 bispecific (Table 22).
Regarding claims 29, 34, and 37-38, Vu 2017 teaches the active steps of the method of treatment of claim 1 and teaches the bispecific anti-BCMA and anti-CD3 bispecific of the claims which applicant shows has the required biological activity of the claims. The bispecific of Vu 2017 would inherently have the biological activity required by claims 29, 34, and 37-38.
Claim Rejections - 35 USC § 103
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.
The factual inquiries 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.
Claims 1, 3, 13, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Vu (WO 2014122144 A1) (IDS), Nakayamada & Tanaka. Inflammation and Regeneration. 36(6):1-6. (2016) (PTO-892), and Frank et. al. Current Opinion in Immunology. 43:39-45. (2016) (PTO-892).
The teachings of Vu from the 102 rejection are incorporated here in full.
Vu teaches bispecific antibodies that bind BCMA and CD3 for use in treatment of autoimmune diseases including systemic lupus erythematosus (SLE) (Examples 3 and 10).
Vu teaches the use of the BCMA binding bispecific antibodies in conditions related to BCMA including autoimmune disorders (page 19 in lines 5-25).
Vu does not teach the use of bispecific BCMA antibodies in the treatment of the ANCA-associated vasculitis (AAV) granulomatosis with poly angiitis (GPA) and does not teach the use of BCMA targeted therapy when AAV is impacting organs.
These deficiencies are filled by Nakayamada and Frank.
Nakayamada teaches that B cells play a pivotal role in autoimmunity through production of pathogenic autoantibodies but also through modulating immune responses via the production of cytokines and chemokines and further teaches the regulation of pathways that include BCMA in the treatment of multiple autoimmune disease (abstract and figure 1). Nakayamada teaches the use of belimumab which inhibits BCMA pathway in the treatment of GPA (Figure 1 and page 4 in col 1 in par 1).
Nakayamada teaches the use of belimumab in cases where major organs are involved (page 1 in col 1 in lines 1-6 and page 4 in col 1 in lines 3-6).
Nakayamada teaches the exploration of B cell-targeted therapies in autoimmune diseases (page 4 in col 2 in “Conclusions”).
Frank teaches B cells has as an effective target for therapeutic intervention in autoimmune disease (abstract). Frank teaches the use of antibodies that bind B cell surface molecules for the treatment of autoimmunity and the first therapeutics using known in the art B cell targeting therapeutics (page 39 in col 2 in par 4). Frank teaches the targeting of BCMA in autoimmune diseases (page 42 in col 1 in par 1-4 and col 1 in lines 1-11).
It would have been obvious at the time the application was filled to substitute the generic BCMA related autoimmune disease treated in the method of Vu with the BCMA related GPA taught by Nakayamada. One of skill in the art would have been motivated to explore further applications of the method of treating autoimmune diseases by administering a bispecific antibody that binds BCMA and CD3 taught by Vu in diseases known to respond to anti-BCMA therapy as taught by Nakayamada. One of skill in the art would see Nakayamada and Frank teachings towards exploring BCMA targeted therapy and Vu teaching towards use of BCMA therapy in autoimmune disease including GPA. There would have been a reasonable expectation of success as Nakayamada teaches BCMA related treatment in autoimmune diseases including GPA and Vu teaches a BCMA targeted therapy for use in autoimmune diseases with known BCMA involvement.
Claims 1, 3, 21-22, and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Vu (WO 2014122144 A1) (IDS), Nakayamada & Tanaka. Inflammation and Regeneration. 36(6):1-6. (2016) (PTO-892), and Frank et. al. Current Opinion in Immunology. 43:39-45. (2016) (PTO-892) as applied to claims 1, 3, 13, and 20-21 above, and further in view of Park. Tuberc Respir Dis. 74(4)::151-162. (2013) (PTO-892).
The teachings of Vu from the previous 102 and 103 rejections are incorporated here in full.
The teachings of Nakayamada and Frank from the previous 103 rejection are incorporated here in full.
Vu in view of Nakayamada and Frank teaches a method of treating autoimmune diseases including SLE and AAV by administering a bispecific antibody that binds BCMA and CD3 as previously described.
Vu in view of Nakayamada and Frank does not teach the treatment of a patient population that has diffuse alveolar hemorrhage (DAH).
This deficiency is filled by Park.
Park teaches DAH presents with hemoptysis, anemia, and diffuse alveolar infiltrates. Most cases of DAH are caused by capillaritis associated with systemic autoimmune disease such as AAV and SLE. Park teaches rapid diagnosis and treatment is crucial for survival in patients. Park further teaches the gold standard of treatment is corticosteroids and immunosuppressive agents (abstract). Park teaches treatment with antibodies that target B-cells (page 157 in col 2 in par 1). Park teaches organ involvement in the patients including the kidneys (Table 2).
Regarding claim 35, Park teaches the treatment includes a maintenance of remission stage (page 156 in col 2 in par 3).
It would have been obvious at the time the application was filed to combine the method of treating SLE and AAV by administering an anti-BCMA anti-CD3 bispecific antibody of Vu in view of Nakayamada and Frank in the AAV and SLE patient population with DAH as taught by Park. One of skill in the art would have been motivated to use a known therapeutic with immunosuppressive activity in a patient population with immediate medical need. Park teaches towards the use of B-cell targeting therapeutics, the need for immediate effective intervention, and the use of antibodies. There would have been a reasonable expectation of success as Vu in view of Nakayamada and Frank teach an effective method of treating patients with SLE and AAV and Park shows the effectiveness of similar therapeutics in a related patient population.
Conclusion
No claims allowable.
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/F.E./Examiner, Art Unit 1643
/Meera Natarajan/Primary Examiner, Art Unit 1643