ALK polypeptides and methods of use thereof
Inventors
LI, Adrienne • EBY, Jackson • DeMuth, Peter C.
Assignees
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Publication Number
US-11623002-B2
Publication Date
2023-04-11
Expiration Date
Abstract
The invention features immunogenic compositions containing anaplastic lymphoma kinase (ALK) polypeptides and methods of use thereof. The immunogenic compositions and methods of the invention may be used to treat a disease associated with ALK in a subject, such as cancer (e.g., a solid tumor cancer or an ALK+ cancer).
Core Innovation
The invention relates to amphiphilic conjugates comprising an albumin-binding domain and an ALK polypeptide, with an optional linker. The ALK polypeptide is 9 to 40 amino acids in length, comprises at least 6 contiguous amino acids from SEQ ID NO: 3, and does not comprise sequences of certain excluded SEQ ID NOs. The ALK polypeptide is conjugated directly to the albumin-binding domain or conjugated through the optional linker.
The albumin-binding domain may be provided as a lipid, and the optional linker may include polymers, a string of amino acids, nucleic acids, polysaccharides, or combinations thereof. Linker types and peptide spacer motifs are described, including glycine/serine motifs and synthetic polymers such as PEG. The disclosure also describes conjugation junctions for the ALK-polypeptide and albumin-binding-domain construct.
The disclosure also describes covalently conjugated ALK polypeptides incorporated into interbilayer-crosslinked multilamellar lipid vesicles (ICMVs). Crosslinking of multilamellar lipid vesicles is described using functionalized lipid headgroups and crosslinkers, and the document further describes amphiphilic conjugates comprising lipid albumin binders and direct or linker-mediated conjugation constraints on the ALK polypeptide sequence content.
The disclosure also includes immunogenic ALK polypeptides and immunogenic compositions intended for treating ALK-associated cancers. The immunogenic ALK polypeptides are mutant and/or fragments of the ALK cytoplasmic domain, framed for eliciting immune responses such as CD8+ cytotoxic T lymphocytes and CD4+ T helper cells. Additional disclosed multi-ALK formats combine three different sequence segments, with allowed combinations described in table content and explicit exclusions of defined sequences.
Claims Coverage
The independent claim set includes the amphiphilic conjugate itself, with defined ALK polypeptide sequence constraints and an albumin-binding domain, plus optional direct or linker-mediated conjugation. Across the independent claim family, there are two inventive features, with dependent claims refining the albumin-binding domain and linker classes and extending to immunogenic and pharmaceutical compositions.
Albumin-binding domain with ALK polypeptide sequence constraints
An amphiphilic conjugate comprising an albumin-binding domain and an ALK polypeptide, wherein the ALK polypeptide is 9 to 40 amino acids in length, comprises at least 6 contiguous amino acids from a sequence of SEQ ID NO: 3, and does not comprise a sequence of any one of SEQ ID NOs: 67-70 and 140-145.
Direct or linker-mediated conjugation to the albumin-binding domain
An amphiphilic conjugate wherein the ALK polypeptide is conjugated directly to the albumin-binding domain or is conjugated to the albumin-binding domain through the linker.
Lipid albumin-binding domain
The amphiphilic conjugate wherein the albumin-binding domain is a lipid.
Optional linker selected from defined linker classes
The amphiphilic conjugate wherein the linker is selected from the group consisting of polymers, a string of amino acids, nucleic acids, polysaccharides, or a combination thereof.
Immunogenic composition comprising the amphiphilic conjugate
An immunogenic composition comprising the amphiphilic conjugate.
Pharmaceutical composition including a therapeutically effective amount
A pharmaceutical composition comprising a therapeutically effective amount of an immunogenic composition and one or more pharmaceutically acceptable carriers or excipients.
Claim coverage centers on an amphiphilic conjugate that couples an albumin-binding domain to a constrained ALK polypeptide using either direct conjugation or an optional linker, with dependent claims further refining the albumin-binding domain as a lipid and specifying linker class options, and then extending the concept to immunogenic and pharmaceutical compositions.
Stated Advantages
Documented Applications
Treating ALK-associated cancers using immunogenic ALK polypeptides and immunogenic compositions framed for vaccine/immunotherapy purposes.
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