Abstract

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.

IPC Classes  ?

• C07K 14/775 - Apolipopeptides
• C12N 9/18 - Carboxylic ester hydrolases
• C12N 9/22 - Ribonucleases
• C12N 15/62 - DNA sequences coding for fusion proteins

Abstract

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.

IPC Classes  ?

• C07K 14/775 - Apolipopeptides
• C07K 19/00 - Hybrid peptides
• C12N 9/18 - Carboxylic ester hydrolases
• C12N 9/22 - Ribonucleases
• C12N 15/62 - DNA sequences coding for fusion proteins

Abstract

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.

IPC Classes  ?

• C12N 9/22 - Ribonucleases
• A61P 11/00 - Drugs for disorders of the respiratory system
• C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
• C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
• A61K 38/00 - Medicinal preparations containing peptides

Abstract

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.

IPC Classes  ?

• C12N 9/22 - Ribonucleases
• A61K 38/00 - Medicinal preparations containing peptides
• A61P 11/00 - Drugs for disorders of the respiratory system
• C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
• C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)

Abstract

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.

IPC Classes  ?

• C12N 9/22 - Ribonucleases
• A61P 11/00 - Drugs for disorders of the respiratory system
• C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
• C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
• A61K 38/00 - Medicinal preparations containing peptides

Abstract

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.

IPC Classes  ?

• C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
• A61K 38/00 - Medicinal preparations containing peptides

Abstract

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.

IPC Classes  ?

• C12N 9/22 - Ribonucleases
• A61K 38/00 - Medicinal preparations containing peptides
• A61P 11/00 - Drugs for disorders of the respiratory system
• C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
• C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)

Abstract

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.

IPC Classes  ?

• C12N 9/22 - Ribonucleases
• A61P 11/00 - Drugs for disorders of the respiratory system
• C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
• C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
• A61K 38/00 - Medicinal preparations containing peptides

Abstract

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.

IPC Classes  ?

• C07K 14/775 - Apolipopeptides
• C12N 9/18 - Carboxylic ester hydrolases
• C12N 9/22 - Ribonucleases
• C12N 15/62 - DNA sequences coding for fusion proteins

Abstract

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.

IPC Classes  ?

• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons

Abstract

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.

IPC Classes  ?

• C12N 9/22 - Ribonucleases
• C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)

Abstract

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.

IPC Classes  ?

• C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
• C12N 9/22 - Ribonucleases

Abstract

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.

IPC Classes  ?

• C07K 14/705 - ReceptorsCell surface antigensCell surface determinants
• C12N 9/02 - Oxidoreductases (1.), e.g. luciferase
• C12N 9/16 - Hydrolases (3.) acting on ester bonds (3.1)
• C12N 9/22 - Ribonucleases
• C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons

Abstract

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.

IPC Classes  ?

• C07K 14/775 - Apolipopeptides
• C12N 9/18 - Carboxylic ester hydrolases
• C12N 9/22 - Ribonucleases
• C12N 15/62 - DNA sequences coding for fusion proteins
• A61K 38/00 - Medicinal preparations containing peptides

Abstract

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.

IPC Classes  ?

• C07K 14/775 - Apolipopeptides
• C12N 15/62 - DNA sequences coding for fusion proteins

Abstract

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.

IPC Classes  ?

• C07K 14/775 - Apolipopeptides
• C07K 19/00 - Hybrid peptides
• C12N 9/18 - Carboxylic ester hydrolases
• C12N 9/22 - Ribonucleases
• C12N 15/62 - DNA sequences coding for fusion proteins

Abstract

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.

IPC Classes  ?

• C07K 14/775 - Apolipopeptides
• C12N 9/18 - Carboxylic ester hydrolases
• C12N 9/22 - Ribonucleases

Abstract

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.

IPC Classes  ?

• C07K 14/775 - Apolipopeptides
• C12N 9/18 - Carboxylic ester hydrolases
• C12N 9/22 - Ribonucleases