Anti-SIRP α antibodies
Inventors
Verheijden, Gijsbertus Franciscus Maria • ROUWENDAL, Gerard • ARENDS, Roland Jan • van den Berg, Timo Kars • MATLUNG, Hanke Lottie • FRANKE, Katarina
Assignees
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Publication Number
US-11718681-B2
Publication Date
2023-08-08
Expiration Date
Abstract
The invention relates to antibodies against SIRPα that are suitable for use in anti-cancer therapy. The invention also relates to the use of the anti-SIRPα antibodies in the treatment of human solid tumours and haematological malignancies, optionally in combination with other anti-cancer therapies.
Core Innovation
The invention relates to anti-SIRPα antibodies and antigen-binding fragments for treating human solid tumours or haematological malignancies in patients whose tumour or malignancy expresses SIRPα. The anti-SIRPα antibodies comprise heavy chain and light chain variable region complementarity determining regions selected from defined groups, where the CDRs are determined according to Kabat numbering. The described antibodies are characterized by antagonistic binding to predominant SIRPα polymorphs, including SIRPαBIT and SIRPα1.
The antibodies are described as not binding SIRPγ, addressing prior shortcomings of anti-SIRPα antibodies that were species specific and/or cross-reactive. The disclosed approach is presented as enhancing Fc-receptor-mediated immune effector functions, including ADCC and ADCP, using the anti-SIRPα antibodies alone or in combination with other anti-cancer therapeutics. The described combinations are intended to improve treatment of cancers expressing SIRPα.
The disclosure further specifies antibody formats and embodiments, including monoclonal antibodies and fragments, with antibody examples including IgG and IgA formats, and humanized antibodies being preferred. It includes pharmaceutical composition and combination-therapy embodiments. The document also specifies Fc engineering to reduce binding to activating human Fcα/Fcγ receptors, including IgG1 Fc substitutions, and provides variable-region CDR sequence sets defined by SEQ ID NOs determined using Kabat numbering.
Claims Coverage
The disclosed independent claims cover two distinct treating methods for cancers expressing SIRPα: administration of anti-SIRPα antibody using defined Kabat-numbered CDR SEQ ID NO combinations, and the same anti-SIRPα treatment combined with one or more other anti-cancer therapeutics. Across the independent claims, the inventive coverage is organized around specified CDR sequence selections and, in the combination claim, the requirement for co-administration of other anti-cancer therapeutics.
Treating SIRPα-expressing human solid tumours or haematological malignancies with Kabat-numbered CDR-selected anti-SIRPα antibody
A method for treating human solid tumours or haematological malignancies by administering an anti-SIRPα antibody or antigen-binding fragment comprising heavy chain and light chain variable region CDRs selected from SEQ ID NO pairs, where the CDRs are determined according to Kabat numbering, and wherein the human solid tumour or haematological malignancy expresses SIRPα.
Combination treatment with anti-SIRPα antibody and one or more other anti-cancer therapeutics with Kabat-numbered CDR-selected CDRs
A method for treating a human solid tumour or haematological malignancy by administering an anti-SIRPα antibody or antigen-binding fragment comprising heavy chain and light chain variable region CDRs selected from SEQ ID NO pairs where the CDRs are determined according to Kabat numbering, and further administering one or more other anti-cancer therapeutics for use in the treatment of the human solid tumour or haematological malignancy.
Overall, the independent claims are directed to treating cancers that express SIRPα using anti-SIRPα antibodies defined by Kabat-numbered heavy- and light-chain CDR SEQ ID NO selections, and to an additional method variant that requires co-administration of one or more other anti-cancer therapeutics.
Stated Advantages
Enhances Fc-receptor-mediated immune effector functions (ADCC and ADCP).
Antagonistic binding to predominant SIRPα polymorphs (SIRPαBIT and SIRPα1).
Avoids binding to SIRPγ, addressing prior shortcomings of species specificity and/or cross-reactivity.
Documented Applications
Treating patients with human solid tumours or haematological malignancies expressing SIRPα using an anti-SIRPα antibody or antigen-binding fragment.
Treating human solid tumours including renal cancer or melanoma using the anti-SIRPα method.
Combination therapy use case: administering the anti-SIRPα antibody together with one or more other anti-cancer therapeutics for treating the human solid tumour or haematological malignancy.
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