Multispecific heavy chain antibodies binding to CD22 and CD3
Inventors
Trinklein, Nathan • RANGASWAMY, UDAYA • Iyer, Suhasini • Prabhakar, Kirthana • Ugamraj, Harshad
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11905326-B2
Publication Date
2024-02-20
Expiration Date
Abstract
Multispecific, human heavy chain antibodies (e.g., UniAbs™) binding to CD22 and CD3 are disclosed, along with methods of making such antibodies, compositions, including pharmaceutical compositions, comprising such antibodies, and their use to treat disorders that are characterized by the expression of CD22.
Core Innovation
The invention relates to multispecific binding compounds comprising a first binding unit with binding affinity to CD22 and a second binding unit with binding affinity to CD3. The CD22-binding unit is defined by a heavy chain variable region comprising specified CDR sequence sets, and the CD3-binding unit is defined by specified heavy chain variable region CDR sequences together with a light chain variable region comprising specified CDR sequences. The multispecific binding compound format is enabled using human heavy chain-only antibody concepts derived from UniAbs/UniRat-derived designs.
The invention further defines heavy chain-only antibodies binding to CD22 using a heavy chain variable region comprising specified CDR1, CDR2, and CDR3 sequence combinations. The disclosed designs include heavy chain variable region sequence definitions based on named SEQ ID sets and framework/variable region specifications, including human VH framework-related limitations and identity constraints. The heavy chain-only antibodies are described as lacking CH1 sequence in the heavy chain constant region and as including human IgG1/IgG4 Fc options in certain embodiments.
In addition, the document discloses therapeutic compositions and therapeutic use for the described CD22- and CD3-binding multispecific compounds, particularly for CD22-expressing B-cell disorders. Stated applications include treating disorders characterized by CD22 expression, including DLBCL/non-Hodgkin's lymphoma, SLE, rheumatoid arthritis, and multiple sclerosis. The document also describes CAR-T and multispecific/bi- or three-chain antibody-like configurations in connection with the binding compounds.
Claims Coverage
The provided independent claims cover three inventive features: a multispecific binding compound with binding units for CD22 and CD3 defined by specific CDR sequence sets, a CD22-binding heavy chain-only antibody defined by specified CD22 CDR sequence sets, and a second multispecific binding compound instance with fixed CD22 and CD3 CDR pairings.
CD22-binding heavy chain variable region defined by selected CDR sequences
A first binding unit with binding affinity to CD22 comprises a heavy chain variable region comprising a CDR1 sequence of SEQ ID NO: 1, a CDR2 sequence selected from SEQ ID NO: 11 or SEQ ID NO: 12, and a CDR3 sequence selected from SEQ ID NO: 18 or SEQ ID NO: 19 or SEQ ID NO: 20.
CD3-binding unit defined by heavy and light chain variable region CDR sequences
A second binding unit having binding affinity to CD3 comprises a heavy chain variable region comprising CDR1 sequence of SEQ ID NO: 85, CDR2 sequence of SEQ ID NO: 86, and CDR3 sequence of SEQ ID NO: 87, together with a light chain variable region comprising CDR1 sequence of SEQ ID NO: 88, CDR2 sequence of SEQ ID NO: 89, and CDR3 sequence of SEQ ID NO: 90.
CD22-binding heavy chain-only antibody defined by selected CDR sequences
A heavy chain-only antibody binding to CD22 comprises a heavy chain variable region comprising a CDR1 sequence of SEQ ID NO: 1, a CDR2 sequence selected from SEQ ID NO: 11 or SEQ ID NO: 12, and a CDR3 sequence selected from SEQ ID NO: 18 or SEQ ID NO: 19 or SEQ ID NO: 20.
CD22/CD3 multispecific binding compound with fixed CDR pairing
A multi-specific binding compound comprises a first binding unit having binding affinity to CD22 with a heavy chain variable region comprising CDR1 sequence of SEQ ID NO: 1, CDR2 sequence of SEQ ID NO: 12, and CDR3 sequence of SEQ ID NO: 19; and a second binding unit having binding affinity to CD3 with a heavy chain variable region comprising CDR1 sequence of SEQ ID NO: 85, CDR2 sequence of SEQ ID NO: 86, and CDR3 sequence of SEQ ID NO: 87, and a light chain variable region comprising CDR1 sequence of SEQ ID NO: 88, CDR2 sequence of SEQ ID NO: 89, and CDR3 sequence of SEQ ID NO: 90.
The claim set is grounded in exact CD22-binding CDR definitions and exact CD3-binding CDR definitions across heavy and light chain variable regions. Independent claim coverage also distinguishes multispecific CD22/CD3 compounds from CD22-binding heavy chain-only antibodies, while maintaining the same core CDR sequence-defined binding units.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating B-cell disorders characterized by CD22 expression by administering a multi-specific binding compound as recited in claim 1.
Treating a B-cell disorder characterized by CD22 expression, including non-Hodgkin's lymphoma (NHL).
Treating B-cell disorders characterized by CD22 expression via pharmaceutical compositions comprising the heavy chain-only antibody binding to CD22.
Interested in licensing this patent?