Abrégé

Compositions and methods relating to ApoA-1 fusion polypeptides are disclosed. The fusion polypeptides include a first polypeptide segment corresponding to an ApoA-1 polypeptide or ApoA-1 mimetic, and may also include a dimerizing domain such as, e.g., an Fc region, which is typically linked carboxyl-terminal to the first polypeptide segment via a flexible linker. In some embodiments, the fusion polypeptide further includes a second polypeptide segment located carboxyl-terminal to the first polypeptide segment and which confers a second biological activity (e.g., an RNase, paraoxonase, platelet-activating factor acetylhydrolase, cholesterol ester transfer protein, lecithin-cholesterol acyltransferase, polypeptide that specifically binds to proprotein convertase subtilisin/kexin type 9, or polypeptide that specifically binds to amyloid beta). Also disclosed are dimeric proteins comprising first and second ApoA-1 fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C07K 14/775 - Apolipopeptides
• C12N 9/18 - Hydrolases agissant sur les esters d'acides carboxyliques
• C12N 9/22 - Ribonucléases
• C12N 15/62 - Séquences d'ADN codant pour des protéines de fusion

Abrégé

Compositions and methods relating to ApoA-1 fusion polypeptides are disclosed. The fusion polypeptides include a first polypeptide segment corresponding to an ApoA-1 polypeptide or ApoA-1 mimetic, and may also include a dimerizing domain such as, e.g., an Fc region, which is typically linked carboxyl-terminal to the first polypeptide segment via a flexible linker. In some embodiments, the fusion polypeptide further includes a second polypeptide segment located carboxyl-terminal to the first polypeptide segment and which confers a second biological activity (e.g., an RNase, paraoxonase, platelet-activating factor acetylhydrolase, cholesterol ester transfer protein, lecithin-cholesterol acyltransferase, polypeptide that specifically binds to proprotein convertase subtilisin/kexin type 9, or polypeptide that specifically binds to amyloid beta). Also disclosed are dimeric proteins comprising first and second ApoA-1 fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C07K 14/775 - Apolipopeptides
• C07K 19/00 - Peptides hybrides
• C12N 9/18 - Hydrolases agissant sur les esters d'acides carboxyliques
• C12N 9/22 - Ribonucléases
• C12N 15/62 - Séquences d'ADN codant pour des protéines de fusion

Abrégé

Compositions and methods relating to paraoxonase fusion polypeptides are disclosed. In some aspects, the fusions are bispecific molecules that include a first biologically active polypeptide linked amino-terminal to a biologically active paraoxonase, wherein the first biologically active polypeptide is a DNase, an RNase, a SOD1, a CTLA-4 extracellular domain, a CD40 extracellular domain, or a polypeptide that specifically binds and neutralizes an inflammatory cytokine. Bispecific fusions may further include a second biologically active polypeptide (e.g., a dimerizing or FcRn-binding domain) linked carboxyl-terminal to the first biologically active polypeptide and amino-terminal to the paraoxonase. In other aspects, a fusion polypeptide includes a biologically active paraoxonase linked carboxyl-terminal or amino-terminal to a dimerizing or FcRn-binding domain. Also disclosed are dimeric proteins comprising first and second paraoxonase fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C12N 9/22 - Ribonucléases
• A61P 11/00 - Médicaments pour le traitement des troubles du système respiratoire
• C07K 16/24 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des cytokines, des lymphokines ou des interférons
• C12N 9/16 - Hydrolases (3.) agissant sur les liaisons esters (3.1)
• A61K 38/00 - Préparations médicinales contenant des peptides

Abrégé

Compositions and methods relating to paraoxonase fusion polypeptides are disclosed. In some aspects, the fusions are bispecific molecules that include a first biologically active polypeptide linked amino-terminal to a biologically active paraoxonase, wherein the first biologically active polypeptide is a DNase, an RNase, a SOD1, a CTLA-4 extracellular domain, a CD40 extracellular domain, or a polypeptide that specifically binds and neutralizes an inflammatory cytokine. Bispecific fusions may further include a second biologically active polypeptide (e.g., a dimerizing or FcRn-binding domain) linked carboxyl-terminal to the first biologically active polypeptide and amino-terminal to the paraoxonase. In other aspects, a fusion polypeptide includes a biologically active paraoxonase linked carboxyl-terminal or amino-terminal to a dimerizing or FcRn-binding domain. Also disclosed are dimeric proteins comprising first and second paraoxonase fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C12N 9/22 - Ribonucléases
• A61K 38/00 - Préparations médicinales contenant des peptides
• A61P 11/00 - Médicaments pour le traitement des troubles du système respiratoire
• C07K 16/24 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des cytokines, des lymphokines ou des interférons
• C12N 9/16 - Hydrolases (3.) agissant sur les liaisons esters (3.1)

Abrégé

Compositions and methods relating to paraoxonase fusion polypeptides are disclosed. In some aspects, the fusions are bispecific molecules that include a first biologically active polypeptide linked amino-terminal to a biologically active paraoxonase, wherein the first biologically active polypeptide is a DNase, an RNase, a SOD1, a CTLA-4 extracellular domain, a CD40 extracellular domain, or a polypeptide that specifically binds and neutralizes an inflammatory cytokine. Bispecific fusions may further include a second biologically active polypeptide (e.g., a dimerizing or FcRn-binding domain) linked carboxyl-terminal to the first biologically active polypeptide and amino-terminal to the paraoxonase. In other aspects, a fusion polypeptide includes a biologically active paraoxonase linked carboxyl-terminal or amino-terminal to a dimerizing or FcRn-binding domain. Also disclosed are dimeric proteins comprising first and second paraoxonase fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C12N 9/22 - Ribonucléases
• A61P 11/00 - Médicaments pour le traitement des troubles du système respiratoire
• C07K 16/24 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des cytokines, des lymphokines ou des interférons
• C12N 9/16 - Hydrolases (3.) agissant sur les liaisons esters (3.1)
• A61K 38/00 - Préparations médicinales contenant des peptides

Abrégé

e.g.e.g., a CTLA-4 extracellular domain or a CD40 extracellular domain) linked amino-terminal to the dimerizing or FcRn-binding domain. Also disclosed are dimeric proteins comprising first and second PON3 or evolved PON1 fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C12N 9/16 - Hydrolases (3.) agissant sur les liaisons esters (3.1)
• A61K 38/00 - Préparations médicinales contenant des peptides

Abrégé

Compositions and methods relating to DNase fusion polypeptides are disclosed. The fusion polypeptides include a biologically active DNase joined to the amino-terminus of an immunoglobulin Fc region via a flexible polypeptide linker (e.g., a linker containing at least 26 amino acid residues). Typically, the DNase is a hyperactive and/or actin-resistant DNase1 variant (e.g., a variant of human DNase1 having one or more amino acid substitutions selected from substitutions at Asp-53, Tyr-65, Glu-69, Arg-74, Gly-105, and Ala-114 according to amino acid position numbering of mature wild-type human DNase1) or a DNase1L3 variant (e.g., a variant of human DNase1L3 in which the native nuclear localization signals are removed). In some embodiments, the fusion polypeptide includes a polypeptide segment located carboxyl-terminal to the Fc region and which may be, e.g., a biologically active paraoxonase. Also disclosed are dimeric proteins comprising first and second DNase fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy, including methods for treating diseases and disorders characterized by NETosis.

Classes IPC  ?

• C12N 9/22 - Ribonucléases
• A61K 38/00 - Préparations médicinales contenant des peptides
• A61P 11/00 - Médicaments pour le traitement des troubles du système respiratoire
• C07K 16/24 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des cytokines, des lymphokines ou des interférons
• C12N 9/16 - Hydrolases (3.) agissant sur les liaisons esters (3.1)

Abrégé

Compositions and methods relating to paraoxonase fusion polypeptides are disclosed. In some aspects, the fusions are bispecific molecules that include a first biologically active polypeptide linked amino-terminal to a biologically active paraoxonase, wherein the first biologically active polypeptide is a DNase, an RNase, a SOD1, a CTLA-4 extracellular domain, a CD40 extracellular domain, or a polypeptide that specifically binds and neutralizes an inflammatory cytokine. Bispecific fusions may further include a second biologically active polypeptide (e.g., a dimerizing or FcRn-binding domain) linked carboxyl-terminal to the first biologically active polypeptide and amino-terminal to the paraoxonase. In other aspects, a fusion polypeptide includes a biologically active paraoxonase linked carboxyl-terminal or amino-terminal to a dimerizing or FcRn-binding domain. Also disclosed are dimeric proteins comprising first and second paraoxonase fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C12N 9/22 - Ribonucléases
• A61P 11/00 - Médicaments pour le traitement des troubles du système respiratoire
• C07K 16/24 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des cytokines, des lymphokines ou des interférons
• C12N 9/16 - Hydrolases (3.) agissant sur les liaisons esters (3.1)
• A61K 38/00 - Préparations médicinales contenant des peptides

Abrégé

Compositions and methods relating to ApoA-1 fusion polypeptides are disclosed. The fusion polypeptides include a first polypeptide segment corresponding to an ApoA-1 polypeptide or ApoA-1 mimetic, and may also include a dimerizing domain such as, e.g., an Fc region, which is typically linked carboxyl-terminal to the first polypeptide segment via a flexible linker. In some embodiments, the fusion polypeptide further includes a second polypeptide segment located carboxyl-terminal to the first polypeptide segment and which confers a second biological activity (e.g., an RNase, paraoxonase, platelet-activating factor acetylhydrolase, cholesterol ester transfer protein, lecithin-cholesterol acyltransferase, polypeptide that specifically binds to proprotein convertase subtilisin/kexin type 9, or polypeptide that specifically binds to amyloid beta). Also disclosed are dimeric proteins comprising first and second ApoA-1 fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C07K 14/775 - Apolipopeptides
• C12N 9/18 - Hydrolases agissant sur les esters d'acides carboxyliques
• C12N 9/22 - Ribonucléases
• C12N 15/62 - Séquences d'ADN codant pour des protéines de fusion

Abrégé

Compositions and methods relating to paraoxonase fusion polypeptides are disclosed. In some aspects, the fusions are bispecific molecules that include a first biologically active polypeptide linked amino-terminal to a biologically active paraoxonase (e.g., human PON1 or a variant thereof), wherein the first biologically active polypeptide is a DNase, an RNase, a SOD1, a CTLA-4 extracellular domain, a CD40 extracellular domain, or a polypeptide that specifically binds and neutralizes an inflammatory cytokine. Bispecific fusions may further include a second biologically active polypeptide (e.g., a dimerizing domain or a domain that specifically binds to the neonatal Fc receptor (FcRn)) linked carboxyl-terminal to the first biologically active polypeptide and amino-terminal to the paraoxonase. In other aspects, a fusion polypeptide includes a biologically active paraoxonase linked carboxyl-terminal or amino-terminal to a dimerizing or FcRn-binding domain. In certain variations, a dimerizing or FcRn-binding domain is an immunoglobulin Fc region. Also disclosed are dimeric proteins comprising first and second paraoxonase fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C07K 14/705 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire
• C07K 16/24 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des cytokines, des lymphokines ou des interférons

Abrégé

e.g.e.g.e.g.e.g., a biologically active paraoxonase. Also disclosed are dimeric proteins comprising first and second DNase fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy, including methods for treating diseases and disorders characterized by NETosis.

Classes IPC  ?

• C12N 9/22 - Ribonucléases
• C12N 9/16 - Hydrolases (3.) agissant sur les liaisons esters (3.1)

Abrégé

Compositions and methods relating to DNase fusion polypeptides are disclosed. The fusion polypeptides include a biologically active DNase joined to the amino-terminus of an immunoglobulin Fc region via a flexible polypeptide linker containing at least 26 amino acid residues. Typically, the DNase is a hyperactive and/or actin-resistant DNase1 variant (e.g., a variant of human DNase1 having one or more amino acid substitutions selected from substitutions at Arg-74, Gly-105, and Ala-114 according to amino acid position numbering of mature wild-type human DNase1) or a DNase1L3 variant (e.g., a variant of human DNase1L3 in which the native nuclear localization signals are removed). In some embodiments, the fusion polypeptide includes a polypeptide segment located carboxyl-terminal to the Fc region and which may be, e.g., a biologically active paraoxonase. Also disclosed are dimeric proteins comprising first and second DNase fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy, including methods for treating diseases and disorders characterized by NETosis.

Classes IPC  ?

• C12N 9/16 - Hydrolases (3.) agissant sur les liaisons esters (3.1)
• C12N 9/22 - Ribonucléases

Abrégé

e.g.e.g.e.g., a dimerizing domain or a domain that specifically binds to the neonatal Fc receptor (FcRn)) linked carboxyl-terminal to the first biologically active polypeptide and amino-terminal to the paraoxonase. In other aspects, a fusion polypeptide includes a biologically active paraoxonase linked carboxyl-terminal or amino-terminal to a dimerizing or FcRn-binding domain. In certain variations, a dimerizing or FcRn-binding domain is an immunoglobulin Fc region. Also disclosed are dimeric proteins comprising first and second paraoxonase fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C07K 14/705 - RécepteursAntigènes de surface cellulaireDéterminants de surface cellulaire
• C12N 9/02 - Oxydoréductases (1.), p. ex. luciférase
• C12N 9/16 - Hydrolases (3.) agissant sur les liaisons esters (3.1)
• C12N 9/22 - Ribonucléases
• C07K 16/24 - Immunoglobulines, p. ex. anticorps monoclonaux ou polyclonaux contre du matériel provenant d'animaux ou d'humains contre des cytokines, des lymphokines ou des interférons

Abrégé

Compositions and methods relating to ApoA-1 fusion polypeptides are disclosed. The fusion polypeptides include a first polypeptide segment corresponding to an ApoA-1 polypeptide or ApoA-1 mimetic, and may also include a dimerizing domain such as, e.g., an Fc region, which is typically linked carboxyl-terminal to the first polypeptide segment via a flexible linker. In some embodiments, the fusion polypeptide further includes a second polypeptide segment located carboxyl-terminal to the first polypeptide segment and which confers a second biological activity (e.g., an RNase, paraoxonase, platelet-activating factor acetylhydrolase, cholesterol ester transfer protein, lecithin-cholesterol acyltransferase, polypeptide that specifically binds to proprotein convertase subtilisin/kexin type 9, or polypeptide that specifically binds to amyloid beta). Also disclosed are dimeric proteins comprising first and second ApoA-1 fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C07K 14/775 - Apolipopeptides
• C12N 9/18 - Hydrolases agissant sur les esters d'acides carboxyliques
• C12N 9/22 - Ribonucléases
• C12N 15/62 - Séquences d'ADN codant pour des protéines de fusion
• A61K 38/00 - Préparations médicinales contenant des peptides

Abrégé

Compositions and methods relating to ApoA-1 fusion polypeptides are disclosed. In particular embodiments, the fusion polypeptides include first and second polypeptide segments joined in tandem via a linker, each segment corresponding to an ApoA-1 polypeptide or ApoA-1 mimetic. Fusion polypeptides may also include a dimerizing domain or domain that specifically binds the neonatal Fc receptor (e.g., an Fc region or albumin), which is typically linked carboxyl-terminal to the second polypeptide segment via a flexible linker. In some embodiments, the fusion polypeptide further includes an additional polypeptide segment conferring a second biological activity (e.g., an RNase, paraoxonase, platelet-activating factor acetylhydrolase, cholesterol ester transfer protein, lecithincholesterol acyltransferase, or polypeptide that specifically binds to amyloid beta). Also disclosed are dimeric proteins comprising first and second ApoA-1 fusion polypeptides comprising a dimerizing domain as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C07K 14/775 - Apolipopeptides
• C12N 15/62 - Séquences d'ADN codant pour des protéines de fusion

Abrégé

Compositions and methods relating to ApoA-1 fusion polypeptides are disclosed. The fusion polypeptides include a first polypeptide segment corresponding to an ApoA-1 polypeptide or ApoA-1 mimetic, and may also include a dimerizing domain such as, e.g., an Fc region, which is typically linked carboxyl-terminal to the first polypeptide segment via a flexible linker. In some embodiments, the fusion polypeptide further includes a second polypeptide segment located carboxyl-terminal to the first polypeptide segment and which confers a second biological activity (e.g., an RNase, paraoxonase, platelet-activating factor acetylhydrolase, cholesterol ester transfer protein, lecithin-cholesterol acyltransferase, polypeptide that specifically binds to proprotein convertase subtilisin/kexin type 9, or polypeptide that specifically binds to amyloid beta). Also disclosed are dimeric proteins comprising first and second ApoA-1 fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C07K 14/775 - Apolipopeptides
• C07K 19/00 - Peptides hybrides
• C12N 9/18 - Hydrolases agissant sur les esters d'acides carboxyliques
• C12N 9/22 - Ribonucléases
• C12N 15/62 - Séquences d'ADN codant pour des protéines de fusion

Abrégé

Compositions and methods relating to ApoA-1 fusion polypeptides are disclosed. The fusion polypeptides include a first polypeptide segment corresponding to an ApoA-1 polypeptide or ApoA-1 mimetic, and may also include a dimerizing domain such as, e.g., an Fc region, which is typically linked carboxyl-terminal to the first polypeptide segment via a flexible linker. In some embodiments, the fusion polypeptide further includes a second polypeptide segment located carboxyl-terminal to the first polypeptide segment and which confers a second biological activity (e.g., an RNase, paraoxonase, platelet-activating factor acetylhydrolase, cholesterol ester transfer protein, lecithin-cholesterol acyltransferase, or polypeptide that specifically binds to amyloid beta). Also disclosed are dimeric proteins comprising first and second ApoA-1 fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C07K 14/775 - Apolipopeptides
• C12N 9/18 - Hydrolases agissant sur les esters d'acides carboxyliques
• C12N 9/22 - Ribonucléases

Abrégé

Compositions and methods relating to ApoA-1 fusion polypeptides are disclosed. The fusion polypeptides include a first polypeptide segment corresponding to an ApoA-1 polypeptide or ApoA-1 mimetic, and may also include a dimerizing domain such as, e.g., an Fc region, which is typically linked carboxyl-terminal to the first polypeptide segment via a flexible linker. In some embodiments, the fusion polypeptide further includes a second polypeptide segment located carboxyl-terminal to the first polypeptide segment and which confers a second biological activity (e.g., an RNase, paraoxonase, platelet-activating factor acetylhydrolase, cholesterol ester transfer protein, lecithin-cholesterol acyltransferase, or polypeptide that specifically binds to amyloid beta). Also disclosed are dimeric proteins comprising first and second ApoA-1 fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy.

Classes IPC  ?

• C07K 14/775 - Apolipopeptides
• C12N 9/18 - Hydrolases agissant sur les esters d'acides carboxyliques
• C12N 9/22 - Ribonucléases