Humanized anti-CD45 antibodies

Inventors

ZHAO, LequnKOTANIDES, Helen

Assignees

Actinium Pharmaceuticals Inc

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Publication Number

US-11981741-B2

Patent

Publication Date

2024-05-14

Expiration Date


Abstract

Provided are humanized anti-human CD45 antibodies and pharmaceutical compositions including the antibodies.

Core Innovation

The invention relates to humanized anti-human CD45 antibodies and huCD45-binding antibody fragments. The antibodies are defined by specific immunoglobulin heavy chain variable region sequences and specific immunoglobulin light chain variable region sequences, including enumerated SEQ ID NOs and defined CDR sets. The invention specifies binding and structural sequence constraints between selected heavy-chain and light-chain components.

For variable-region-defined embodiments, the heavy chain variable region comprises SEQ ID NO:2, SEQ ID NO:7, SEQ ID NO:12, SEQ ID NO:17, or SEQ ID NO:22, while the light chain variable region comprises SEQ ID NO:28, SEQ ID NO:33, SEQ ID NO:38, SEQ ID NO:43, or SEQ ID NO:48. The invention further provides an exclusion rule: when the heavy chain variable region comprises SEQ ID NO:2, the light chain variable region is not SEQ ID NO:28.

For CDR-defined embodiments, the invention defines antibodies by enumerated sets of immunoglobulin heavy chain complementarity determining regions and immunoglobulin light chain complementarity determining regions. The invention also documents binding affinity data and use contexts involving radiolabeled and chelator-conjugated CD45-targeting applications, including chelator-conjugated radiopharmaceutical compositions and radiotracer biodistribution approaches.

Claims Coverage

The supplied excerpts include two independent claim families. One covers variable-region-defined anti-huCD45 antibodies with an explicit heavy/light exclusion constraint, and the other covers CDR-defined anti-huCD45 antibodies with enumerated heavy- and light-chain CDR sequence set selections.

Anti-huCD45 antibody defined by variable-region SEQ ID constraints

An anti-huCD45 antibody or huCD45-binding antibody fragment comprising an immunoglobulin heavy chain variable region comprising SEQ ID NO:17, SEQ ID NO:7, SEQ ID NO:12, SEQ ID NO:22, or SEQ ID NO:2 and an immunoglobulin light chain variable region comprising SEQ ID NO:43, SEQ ID NO:48, SEQ ID NO:33, SEQ ID NO:38, or SEQ ID NO:28, with the provision that when the heavy chain variable region comprises SEQ ID NO:2, the light chain variable region is not SEQ ID NO:28.

Anti-huCD45 antibody defined by paired heavy- and light-chain CDR sets

An anti-huCD45 antibody or huCD45-binding antibody fragment comprising immunoglobulin heavy chain complementarity determining regions selected from enumerated sets and immunoglobulin light chain complementarity determining regions selected from enumerated sets, including SEQ ID NO:53 with SEQ ID NO:58, SEQ ID NO:56, or SEQ ID NO:57, together with light-chain selections using SEQ ID NO:59, SEQ ID NO:63, SEQ ID NO:61, and alternative selections involving SEQ ID NO:64 or SEQ ID NO:62/SEQ ID NO:60 while retaining SEQ ID NO:61 for CDR3 in the listed sets.

Overall, the claim coverage centers on anti-huCD45 antibodies or huCD45-binding antibody fragments defined by specific heavy- and light-chain variable region SEQ ID selections with an exclusion rule, and by specific enumerated heavy- and light-chain CDR sequence sets.

Stated Advantages

Not explicitly described in patent.

Documented Applications

Radiolabeled and chelator-conjugated CD45-targeting uses, including radiopharmaceutical compositions with radionuclides and chelator conjugates [procedural detail omitted for safety].

Antibody-drug conjugate (ADC) CD45-targeting uses [procedural detail omitted for safety].

In vitro binding/assay context involving flow cytometry binding to AML cell lines [procedural detail omitted for safety].

Tumor targeting/biodistribution context involving Indium-111 in HL60 xenograft biodistribution [procedural detail omitted for safety].

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