Biogen's felzartamab receives first global approval in China for treating multiple myeloma and analysis on felzartamab patents

Felzartamab, an anti-CD38 monoclonal antibody, developed by MorphoSys now acquired by Novartis has won its first global approval in China for treating multiple myeloma (MM) in combination with lenalidomide and dexamethasone in adults who have received at least one prior line of therapy. Human Immunology Bioscences (HI-Bio) obtained exclusive licensing rights to develop and commercialize felzartamab outside Greater China and was later acquired by Biogen in July 2024. With the acquisition of TJ Bio’s exclusive licensing rights to felzartamab in Greater China in 2026, Biogen now owns exclusive rights to develop and commercialize the antibody drug globally.

Multiple Myeloma represents 2% of all cancers and 10% of all hematological malignancies. It is caused by malignant B cell developing into cancerous plasma cells which accumulate in the bone marrow and crowd out healthy blood-making processes. As the disease progresses, symptoms such as anemia and thrombocytopenia start to develop and multiple tumors and lesions form throughout the skeletal system. CD38 is an antigen highly expressed on MM cells but to a lower extent on normal cells. Functioning as a receptor and ectoenzymatic transmembrane glycoprotein, CD38 has been selected as the ideal target for depleting myeloma cells and prompted the development of anti-CD38 antibodies in treating MM. Two anti-CD38 have been previously approved in the US for treating MM including fully human daratumumab (2016) and chimeric isatuximab-irfc (2020). Both anti-CD38 drugs are approved as a second-line therapy in combination with dexamethasone and lenalidomide/bortezomib (daratumumab), pomalidomide/carfilzomib (isatuximab-irfc).

Treatment for multiple myeloma (MM) using Felzartamab is protected by the MorphoSys patents US 10,533,057 B2 and US 11,591,406 B2 (a continuation of the ’057 patent). The ’057 patent was filed as an international application under PCT on May 13, 2016 with the EPO as the receiving office under PCT No. PCT/EP2016/060810, which claims priority to the European patent EP 15167597 filed on May 13, 2015. The PCT application was published by WIPO as WO 2016/180958 at 18 months from the May 13, 2015 priority on Nov 17, 2016, and entered the US national stage more than two weeks prior to the 30-month deadline on Oct 26, 2017 as US application 15/569,495. The ’057 patent issued from the ’495 application on Jan 14, 2020. Prior to the ’057 issuance, a continuation application 16/693,904 was filed on Nov 25, 2019 and eventually issued as the ’406 patent on Feb 28, 2023.

The published PCT application covers product claims to the Felzartamab (disclosed as MOR202) of specific sequences (6 CDR sequences) for use in the treatment of MM with limitations on specific dosing regimens (claim 1 & 2), duration (claim 3 & 4) and route (claim 5 & 6), 2 additional heavy chain sequences (claim 7), Fc component (claim 8), and combination treatment with dexamethasone (claim 9 and 10) as supported by the embodiments in the specification. After examining, only 5 claims survived in the ’057 patent at issue. The issued independent claim 1 directs to a method of treating relapsed/refractory MM in humans using the antibody defined by the same recited sequences, combining original limitations in the PCT application on dosage from the original claim 2, duration from claim 4, and combination treatment from claim 10. The dosage originally claimed in the independent claim 1 of 8 mg/kg or more is canceled, along with the canceling of the original claim 3 and 9. The original claims 5-8 are converted to method claims and issued as dependent claims 2-5. In the ’406 continuation patent, the independent claim 1 is directed to treating any multiple myeloma with the deletion of the refractory/relapsed clause (moved to dependent claim 7) using an antibody with specific variable heavy (VH) and variable light (VL) sequences. The comparator clause in the parent independent claim only includes patients treated q1w, which is further limited to q1w or q2w in the continuation independent claim. The dose of 16 mg/kg or more in the parent independent claim is further limited to 16 mg/kg and the duration of q1w over at least 8 weeks is moved to dependent claim 2. Dependent claim 3-4 contain the original limitation in claim 2-3 on intravenous administration and dependent claim 5 contains the original limitation in claim 5 on comprising an IgG1 Fc region. The dexamethasone dosage of 20 mg or 40 mg q1w is moved to dependent claim 6.

The doubling of dosage and the inclusion of the comparator clause arose during the US patent examination, indicating that the superior efficacy was used as an unexpected result to give rise to the patentability of the treatment method. The continuation patent recites an antibody by its VH and VL region and covers a narrower dosage due to the elimination of the open range from 16 mg/kg upwards, with further modifications to the treatment group in comparison. Both patents were awarded patent term adjustments, resulting in expiry on Aug 27, 2036 and Oct 16, 2037 for the parent and continuation patent, respectively. With the first global regulatory clearance in August 2026, Biogen has roughly 10 years to obtain approval for and commercially benefit from the patents on MM treatment using felzartamab outside the Greater China region before biosimilars enter the market. The use of felzartamab in other indications are being examined in ongoing phase 3 clinical trials, for example, in late antibody-mediated rejection (AMR) in kidney transplant under the TRANSCEND trial, IgA nephropathy (IgAN) under the PREVAIL trial, and primary membranous nephropathy (PMN) under the PROMINENT trial. Patents assigned to MorphoSys are currently pending for the AMR (US20240228654A9), IgAN (US20240109977A1), and PMN (US20240343822A1) indications.