Antibodies to Andes hantavirus, and methods for using same
Inventors
Barria, Maria Ines • Ramirez, Jose Luis Garrido • Caceres, Felipe Edgardo Bravo
Assignees
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Publication Number
US-12054536-B2
Publication Date
2024-08-06
Expiration Date
Abstract
This invention provides isolated human antibodies and recombinant proteins comprising defined heavy chains and light chains, wherein the antibodies and recombinant proteins neutralize Andes Virus with defined IC50 values. This invention also provides related pharmaceutical compositions, treatment methods and kits.
Core Innovation
The patent discloses isolated human anti-Andes Virus antibodies comprising two heavy chains and two light chains, including exemplary antibodies MIB22 and JL16. Each antibody is defined by variable region amino acid sequences set forth in SEQ ID NO:2 and SEQ ID NO:4, respectively, and is characterized by Andes Virus neutralization with an IC50 below 2.0 μg/ml.
The invention further provides recombinant protein embodiments comprising an Andes Virus-binding domain with two polypeptide chains, where the first chain comprises a region having an amino acid sequence set forth in SEQ ID NO:2 and the second chain comprises a region having an amino acid sequence set forth in SEQ ID NO:4. These recombinant protein embodiments are also characterized by neutralizing Andes Virus with an IC50 below 2.0 μg/ml.
Compositions comprising the antibody or recombinant protein together with a pharmaceutically acceptable carrier are disclosed for intravenous administration to reduce Andes Virus disease likelihood or to treat symptomatic infected subjects. The disclosed methods include prophylactic reduction of the likelihood of becoming symptomatic after exposure and therapeutic treatment of human subjects who are infected with Andes Virus and symptomatic.
Claims Coverage
The independent claim set comprises six independent methods covering prophylaxis after exposure and treatment after symptomatic Andes Virus infection, using either a human antibody or a recombinant protein with specified variable-region/chain regions and a neutralization activity constraint. Across these independent claims, the inventive features focus on the specified sequence-defined antibody or recombinant protein, Andes Virus neutralization with IC50 below 2.0 μg/ml, and intravenous administration of an effective amount with a pharmaceutically acceptable carrier.
Reducing symptomatic likelihood using a sequence-defined human antibody for exposed subjects
A method for reducing the likelihood of a human subject's becoming symptomatic of an Andes Virus infection by intravenously administering an effective amount of a composition comprising a pharmaceutically acceptable carrier and a human antibody having two heavy chains and two light chains with variable regions set forth in SEQ ID NO:2 and SEQ ID NO:4, wherein the antibody neutralizes Andes Virus with an IC50 below 2.0 μg/ml.
Reducing symptomatic likelihood using a recombinant protein for exposed subjects
A method for reducing the likelihood of a human subject's becoming symptomatic of an Andes Virus infection by intravenously administering an effective amount of a composition comprising a pharmaceutically acceptable carrier and a recombinant protein comprising an Andes Virus-binding domain with two polypeptide chains having regions set forth in SEQ ID NO:2 and SEQ ID NO:4, wherein the protein neutralizes Andes Virus with an IC50 below 2.0 μg/ml.
Reducing symptomatic likelihood using a sequence-defined human antibody for recently exposed subjects
A method for reducing the likelihood of a human subject's becoming symptomatic of an Andes Virus infection by intravenously administering an effective amount of a composition comprising a pharmaceutically acceptable carrier and a human antibody having two heavy chains and two light chains with variable regions set forth in SEQ ID NO:2 and SEQ ID NO:4, wherein the antibody neutralizes Andes Virus with an IC50 below 2.0 μg/ml.
Reducing symptomatic likelihood using a recombinant protein for recently exposed subjects
A method for reducing the likelihood of a human subject's becoming symptomatic of an Andes Virus infection by intravenously administering an effective amount of a composition comprising a pharmaceutically acceptable carrier and a recombinant protein comprising an Andes Virus-binding domain with two polypeptide chains having regions set forth in SEQ ID NO:2 and SEQ ID NO:4, wherein the protein neutralizes Andes Virus with an IC50 below 2.0 μg/ml.
Treating symptomatic infected subjects using a sequence-defined human antibody
A method for treating a human subject who is infected with Andes Virus and symptomatic by intravenously administering an effective amount of a composition comprising a pharmaceutically acceptable carrier and a human antibody having two heavy chains and two light chains with variable regions set forth in SEQ ID NO:2 and SEQ ID NO:4, wherein the antibody neutralizes Andes Virus with an IC50 below 2.0 μg/ml.
Treating symptomatic infected subjects using a recombinant protein
A method for treating a human subject who is infected with Andes Virus and symptomatic by intravenously administering an effective amount of a composition comprising a pharmaceutically acceptable carrier and a recombinant protein comprising an Andes Virus-binding domain with two polypeptide chains having regions set forth in SEQ ID NO:2 and SEQ ID NO:4, wherein the protein neutralizes Andes Virus with an IC50 below 2.0 μg/ml.
Across the independent claims, claim coverage centers on prophylaxis after exposure or recent exposure and therapy for symptomatic Andes Virus infection using intravenous administration of an effective amount of a composition containing either a sequence-defined human antibody or a sequence-defined recombinant Andes Virus-binding protein. Both antibody and recombinant protein embodiments are constrained by Andes Virus neutralization activity defined as an IC50 below 2.0 μg/ml.
Stated Advantages
Reduces the likelihood of a human subject becoming symptomatic of an Andes Virus infection.
Treats a human subject who is infected with Andes Virus and symptomatic of that infection.
Documented Applications
Prophylactic reduction of the likelihood of becoming symptomatic in a human subject at risk of exposure to Andes Virus.
Therapeutic treatment of symptomatic human subjects infected with Andes Virus.
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