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US 2022/0064298 A1Published application
COMPOSITIONS AND METHODS RELATED TO ENGINEERED Fc-ANTIGEN BINDING DOMAIN CONSTRUCTS TARGETED TO CTLA-4
AssigneeMomenta Pharmaceuticals, Inc.
InventorsAnthony Manning, Jonathan C. Lansing, Daniel Ortiz, Laura Rutitzky
Life of this patent
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Abstract
Fc-antigen binding constructs having a CTLA-4 binding domain and two or more Fc domains are described as are methods for using such constructs. Also described are polypeptides making up such constructs. Fc domain monomers that are included in the constructs can include amino acid substitutions that promote homodimerization or heterodimerization
Claims37
An Fc-antigen binding domain construct comprising a CTLA4 binding domain and a first Fc domain joined to a second Fc domain by a linker, wherein each of the first and second Fc domains comprise either a heterodimerizing selectivity module or a homodimerizing selectivity module.
A polypeptide comprising an CTLA binding domain;
- a linker;
- a first IgG1 Fc domain monomer comprising a hinge domain, a CH2 domain and a CH3 domain;
- a second linker;
- a second IgG1 Fc domain monomer comprising a hinge domain, a CH2 domain and a CH3 domain;
- an optional third linker;
- and an optional third IgG1 Fc domain monomer comprising a hinge domain, a CH2 domain and a CH3 domain, wherein at least two Fc domain monomers comprise either a heterodimerizing selectivity module or a homodimerizing selectivity module.
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A polypeptide comprising:
- an CTLA4 binding domain;
- a linker;
- a first IgG1 Fc domain monomer comprising a hinge domain, a CH2 domain and a CH3 domain;
- a second linker;
- a second IgG1 Fc domain monomer comprising a hinge domain, a CH2 domain and a CH3 domain;
- an optional third linker;
- and an optional third IgG1 Fc domain monomer comprising a hinge domain, a CH2 domain and a CH3 domain,
- wherein at least one Fc domain monomer comprises one, two or three reverse charge amino acid mutations.
5 more elements
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An Fc-antigen binding domain construct comprising:
- a) a first polypeptide comprising:
- i) a first Fc domain monomer,
- ii) a second Fc domain monomer
- iii) a first CTLA-4 heavy chain binding domain, and
- iv) a linker joining the first and second Fc domain monomers;
- b) a second polypeptide comprising:
- i) a third Fc domain monomer,
- ii) a fourth Fc domain monomer
- iii) a second CTLA-4 heavy chain binding domain and
- iv) a linker joining the third and fourth Fc domain monomers;
- c) a third polypeptide comprising a fifth Fc domain monomer;
- d) a fourth polypeptide comprising a sixth Fc domain monomer;
- e) a fifth polypeptide comprising a first CTLA-4 light chain binding domain;
- and
- f) a sixth polypeptide comprising a second CTLA-4 light chain binding domain;
- wherein the first and third Fc domain monomers together form a first Fc domain, the second and fifth Fc domain monomers together form a second Fc domain, the fourth and sixth Fc monomers together form a third Fc domain, the first CTLA-4 heavy chain binding domain and first CTLA-4 light chain binding domain together form a first Fab;
- and the second CTLA-4 heavy chain binding domain and second CTLA-4 light chain binding domain together form a second Fab.
14 more elements
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An Fc-antigen binding domain construct comprising:
- a) a first polypeptide comprising:
- i) a first Fc domain monomer,
- ii) a second Fc domain monomer
- iii) a first CTLA-4 heavy chain binding domain, and
- iv) a linker joining the first and second Fc domain monomers;
- b) a second polypeptide comprising:
- i) a third Fc domain monomer,
- ii) a fourth Fc domain monomer
- iii) a second CTLA-4 heavy chain binding domain and
- iv) a linker joining the third and fourth Fc domain monomers;
- c) a third polypeptide comprising a fifth Fc domain monomer and a first CTLA-4 light chain binding domain;
- and
- d) a fourth polypeptide comprising a sixth Fc domain monomer and a second CTLA-4 light chain binding domain;
- wherein the first and third Fc domain monomers together form a first Fc domain, the second and fifth Fc domain monomers together form a second Fc domain, the fourth and sixth Fc monomers together form a third Fc domain, the first CTLA-4 heavy chain binding domain and first CTLA-4 light chain binding domain together form a first Fab;
- and the second CTLA-4 heavy chain binding domain and second CTLA-4 light chain binding domain together form a second Fab.
12 more elements
An Fc-antigen binding domain construct, comprising:
- a) a first polypeptide comprising:
- i) a first Fc domain monomer,
- ii) a second Fc domain monomer
- iii) a first CTLA-4 heavy chain binding domain, and
- iv) a linker joining the first and second Fc domain monomers;
- b) a second polypeptide comprising:
- i) a third Fc domain monomer,
- ii) a fourth Fc domain monomer
- iii) a second CTLA-4 heavy chain binding domain and
- iv) a linker joining the third and fourth Fc domain monomers;
- c) a third polypeptide comprising a fifth Fc domain monomer;
- d) a fourth polypeptide comprising a sixth Fc domain monomer;
- e) a fifth polypeptide comprising a first CTLA-4 light chain binding domain;
- and
- f) a sixth polypeptide comprising a second CTLA-4 light chain binding domain;
- wherein the first and fifth Fc domain monomers together form a first Fc domain, the third and sixth Fc domain monomers together form an second Fc domain, the second and fourth Fc monomers together form a third Fc domain, the first CTLA-4 heavy chain binding domain and first CTLA-4 light chain binding domain together form a first Fab;
- and the second CTLA-4 heavy chain binding domain and second CTLA-4 light chain binding domain together form a second Fab.
14 more elements
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An Fc-antigen binding domain construct, comprising:
- a) a first polypeptide comprising:
- i) a first Fc domain monomer,
- ii) a second Fc domain monomer,
- iii) a linker joining the first and second Fc domain monomers, and
- b) a second polypeptide comprising:
- i) a third Fc domain monomer,
- ii) a fourth Fc domain monomer
- iii) a linker joining the third and fourth Fc domain monomers;
- c) a third polypeptide comprising a fifth Fc domain monomer and a first CTLA-4 heavy chain binding domain and;
- d) a fourth polypeptide comprising a sixth Fc domain monomer a second CTLA-4 heavy chain binding domain;
- e) a fifth polypeptide comprising a first CTLA-4 light chain binding domain;
- and
- f) a sixth polypeptide comprising a second CTLA-4 light chain binding domain;
- wherein the first and fifth Fc domain monomers together form a first Fc domain, the third and sixth Fc domain monomers together form an second Fc domain, the second and fourth Fc domain monomers together form a third Fc domain, the first CTLA-4 heavy chain binding domain and first CTLA-4 light chain binding domain together form a first Fab;
- and the second CTLA-4 heavy chain binding domain and second CTLA-4 light chain binding domain together form a second Fab.
12 more elements
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Dependencies are inferred from the claim text.