Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12116390-B2
Publication Date
2024-10-15
Expiration Date
Abstract
The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising IL-10 or IL-10 variant molecules fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.
Core Innovation
The invention relates to a dual cytokine fusion protein of formula (I), in which a monomeric IL-10 is positioned at both ends of a defined architecture. The architecture links an IL-10 segment to antibody-derived variable regions (X1 and X2) arranged as VL or VH segments, and further includes an additional cytokine segment Z that is inserted between the variable regions. The formula specifies an integer n of 1 for the cytokine segment Z and defines a C-terminal and N-terminal arrangement of the IL-10 monomers.
In one described embodiment, X1 and X2 are derived from a first monoclonal antibody that is an anti-Ebola antibody. The VL and VH from the anti-Ebola antibody include 3 light chain CDRs and 3 heavy chain CDRs that are engrafted with 3 light chain CDRs and 3 heavy chain CDRs from a second monoclonal antibody. In this embodiment, the second antibody is an anti-PD-L1 monoclonal antibody, and Z is IL-2, resulting in an IL-10-based dual cytokine fusion protein with antibody variable regions containing an explicit CDR engrafting scheme.
The disclosed architecture specifies that IL-10 is SEQ ID No: 16, with the dual cytokine fusion protein formed by linking IL-10 monomers through an antibody-derived VL/VH region and an IL-2 cytokine segment, while maintaining a defined arrangement depending on whether X1 is a VL or VH. The fusion protein arrangement is expressed as IL-10-(X1)-(Z^n)-(X2)-IL-10 within formula (I), and dependent claims further narrow the source of the antibody framework regions and the number of CDRs engrafted. The document also states that the fusion protein can be included in a pharmaceutical composition with pharmaceutically acceptable buffers and excipients.
Claims Coverage
The document contains one independent claim, supported by dependent claims that refine the dual-cytokine fusion protein architecture and, in one case, add a pharmaceutical-composition limitation. The independent claim is centered on the formula (I) architecture linking monomeric IL-10, an antibody-derived VL/VH region from an anti-Ebola antibody, and a second cytokine Z other than IL-10.
Dual cytokine fusion protein architecture of formula (I)
A dual cytokine fusion protein of formula (I) in which a monomeric IL-10 is linked to an antibody-derived VL or VH region (X1), an intermediate cytokine segment Z other than IL-10 (with n=1), a second antibody-derived VL or VH region (X2), and a second monomeric IL-10; wherein X1 and X2 correspond to VL/VH arrangement, the first monoclonal antibody is an anti-Ebola antibody, and IL-10 is SEQ ID No: 16 with Z specified as IL-2 and the second antibody specified as an anti-PD-L1 monoclonal antibody.
CDR-engrafting scheme for variable regions using defined CDR counts
The VL and VH from the anti-Ebola antibody include 3 light chain CDRs and 3 heavy chain CDRs that are engrafted with 3 light chain CDRs and 3 heavy chain CDRs from a second monoclonal antibody.
CDR-engrafting for VH/VL framework regions from a human anti-Ebola antibody
The VH and VL regions include framework regions derived from a human anti-Ebola antibody, as part of the fusion protein.
CDR framework grafting with exact numbers from an anti-PD-L1 monoclonal antibody
The fusion protein includes a grafting arrangement where the framework region from the anti-Ebola antibody is grafted with three VH CDRs and three VL CDRs from the anti-PD-L1 monoclonal antibody.
Pharmaceutical composition including the dual cytokine fusion protein
A pharmaceutical composition including the dual cytokine fusion protein together with pharmaceutically acceptable buffers and excipients.
Across the independent and dependent claims, the inventive coverage is concentrated on a specific dual-cytokine fusion protein formula architecture with two monomeric IL-10 units, an antibody-derived VL/VH region from an anti-Ebola antibody, an intermediate cytokine Z that is IL-2 (with n=1), and an explicit CDR engrafting arrangement using defined CDR counts from an anti-PD-L1 monoclonal antibody. Dependent claims further restrict the framework-source to a human anti-Ebola antibody and require exact CDR numbers, and one dependent claim adds a pharmaceutical composition limitation including buffers and excipients.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?