Therapeutic compositions comprising microbe-targeting molecules and their use in methods of preventing and treating infectious disease
AssigneeMiraki Innovation Think Tank LLC
InventorsChristopher VELIS, Keith CRAWFORD
Life of this patent
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Abstract
The present invention provides compositions comprising microbe-targeting molecules (MTMs) that bind microbe-associated molecular patterns, and methods of using the compositions in the prevention and treatment of infectious disease.
Claims23
A composition comprising a collectin-based engineered microbe-targeting molecule (MTM) comprising at least one collectin microbe-binding domain and at least one additional domain, wherein
- the collectin microbe-binding domain comprises the carbohydrate recognition domain (CRD) of a collectin selected from the group consisting of
- (i) mannose-binding lectin (MBL),
- (ii) surfactant protein A (SP-A),
- (iii) surfactant protein D (SP-D),
- (iv) collectin liver 1 (CL-L1),
- (v) collectin placenta 1 (CL-P1),
- (vi) conglutinin collectin of 43 kDa (CL-43),
- (vii) collectin of 46 kDa (CL-46),
- (viii) collectin kidney 1 (CL-K1),
- (ix) conglutinin, and
- (x) a sequence variant having at least 85% sequence identity to any one of (i)-(ix), and wherein the at least one additional domain is one or more domains selected from the group consisting of
- (xi) a collectin cysteine-rich domain,
- (xii) a collectin collagen-like domain,
- (xiii) a collectin coiled-coil neck domain,
- (xiv) a ficolin short N-terminal domain,
- (xv) a ficolin collagen-like domain,
- (xvi) a TLR transmembrane helix,
- (xvii) a TLR C-terminal cytoplasmic signaling domain,
- (xviii) an oligomerization domain,
- (xix) a signal domain,
- (xx) an anchor domain,
- (xxi) a collagen-like domain,
- (xxii) a fibrinogen-like domain,
- (xxiii) an immunoglobulin domain,
- (xxiv) an immunoglobulin-like domain, and
- (xxv) a sequence variant having at least 85% sequence identity to any one of (xi)-(xxiv).
A composition comprising a ficolin-based engineered microbe-targeting molecule (MTM) comprising at least one ficolin microbe-binding domain and at least one additional domain, wherein
- the ficolin microbe-binding domain comprises the fibrinogen-like domain of a ficolin selected from the group consisting of
- (i) ficolin 1,
- (ii) ficolin 2,
- (iii) ficolin 3, and
- (iv) a sequence variant having at least 85% sequence identity to any one of (i)-(iii), and wherein the at least one additional domain is one or more domains selected from the group consisting of
- (v) a ficolin short N-terminal domain,
- (vi) a ficolin collagen-like domain,
- (vii) a collectin cysteine-rich domain,
- (viii) a collectin collagen-like domain,
- (ix) a collectin coiled-coil neck domain,
- (x) a TLR transmembrane helix,
- (xi) a TLR C-terminal cytoplasmic signaling domain,
- (xii) an oligomerization domain,
- (xiii) a signal domain,
- (xiv) an anchor domain,
- (xv) a collagen-like domain,
- (xvi) a fibrinogen-like domain,
- (xvii) an immunoglobulin domain,
- (xviii) an immunoglobulin-like domain, and
- (xix) a sequence variant having at least 85% sequence identity to any one of (v)-(xviii).
A composition comprising a toll-like receptor (TLR)-based engineered microbe-targeting molecule (MTM) comprising at least one TLR microbe-binding domain and at least one additional domain, wherein
- the TLR microbe-binding domain comprises the N-terminal ligand-binding domain of a TLR selected from the group consisting of
- (i) TLR1,
- (ii) TLR2,
- (iii) TLR3,
- (iv) TLR4,
- (v) TLR5,
- (vi) TLR6,
- (vii) TLR7,
- (vii) TLR8,
- (viii) TLR9,
- (ix) TLR10, and
- (x) a sequence variant having at least 85% sequence identity to any one of (i)-(ix), and wherein the at least one additional domain is one or more domains selected from the group consisting of
- (xi) a TLR transmembrane helix,
- (xii) a TLR C-terminal cytoplasmic signaling domain,
- (xiii) a ficolin short N-terminal domain,
- (xiv) a ficolin collagen-like domain,
- (xv) a collectin cysteine-rich domain,
- (xvi) a collectin collagen-like domain,
- (xvii) a collectin coiled-coil neck domain,
- (xviii) an oligomerization domain,
- (xix) a signal domain,
- (xx) an anchor domain,
- (xxi) a collagen-like domain,
- (xxii) a fibrinogen-like domain,
- (xxiii) an immunoglobulin domain,
- (xxiv) an immunoglobulin-like domain, and
- (xxv) a sequence variant having at least 85% sequence identity to any one of (xi)-(xxiv).
The composition according to any preceding claim, wherein at least a portion of the composition is encapsulated in at least one liposome.
The composition according to any preceding claim, wherein the composition comprises an aerosol, a rinse, a spray, a cream, a powder, or an ointment formulated for nasal, oral, and/or ocular administration.
A method of treating an infectious disease in a subject comprising administering a therapeutically-effective amount of a composition of any preceding claim to a subject having an infectious disease.
A method of preventing an infectious disease in a subject comprising administering a therapeutically-effective amount of a composition of any preceding claim to a subject at risk of developing an infectious disease.
Dependencies are inferred from the claim text.