Filovirus antibodies and methods

Inventors

Durvasula, RaviBradfute, StevenKunamneni, Adinarayana

Assignees

US Department of Veterans AffairsUNM Rainforest Innovations

Publication Number

US-12265081-B2

Publication Date

2025-04-01

Expiration Date

2040-03-04

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Abstract

An antibody that binds to a filovirus glycoprotein generally includes include a complementarity determining region (CDR) of any one of SEQ ID NO:27-36 or a combination of such CDRs. The antibody may be used in to detect filovirus in a biological sample obtained from a subject. The antibody also may be formulated into a pharmaceutical composition for administering to a subject having, or at risk of having, a filovirus infection.

Core Innovation

This disclosure describes antibodies that bind to filovirus glycoproteins, specifically including a complementarity determining region (CDR) of any one of SEQ ID NO:27-36 or combinations thereof. The antibodies may be full-length or fragments such as single-chain variable fragments (scFvs). In particular, two scFvs (scFv4-2 and scFv22-1) were identified to strongly bind glycoproteins from diverse filoviruses including ebolaviruses and marburgvirus.

The invention addresses the significant public health challenge posed by filoviruses, which cause highly lethal hemorrhagic fevers with high fatality rates. Early symptoms mimic more common diseases, creating a need for rapid, broad-spectrum detection methods. Current approaches may not adequately detect all filovirus species promptly, thus the invention provides broadly cross-reactive antibodies for diagnostic and therapeutic use.

The invention further includes methods of detecting filovirus in biological samples by contacting the sample with these filovirus-binding antibodies under effective conditions to form antibody:target complexes, detectable by ELISA, Western blot, or immunofluorescence. Also described are therapeutic methods involving administering pharmaceutical compositions containing these antibodies to subjects having or at risk of filovirus infections, including prophylactic and treatment applications.

Claims Coverage

The patent contains one independent antibody composition claim and two independent method claims focused on filovirus detection and treatment. The main inventive features relate to the filovirus glycoprotein-binding antibody composition, detection methods using this antibody, and therapeutic administration of the antibody.

Antibody comprising specific CDRs of scFv4-2

An antibody that comprises Complementarity Determining Regions 1, 2, and 3 of the variable heavy chain and variable light chain of EbovGPscFv4-2 (SEQ ID NO:30).

Method of detecting filovirus in a biological sample

A method involving obtaining a biological sample from a subject, contacting it with the antibody comprising scFv4-2 CDRs under conditions effective to bind filovirus, forming an antibody:target complex, and detecting this complex by ELISA, Western blot analysis, or immunofluorescence assay.

Method of treating a subject with filovirus infection or at risk thereof

Administering to the subject an effective amount of a pharmaceutical composition comprising the antibody with scFv4-2 CDRs, either prophylactically before symptoms or therapeutically after symptoms of filovirus infection manifest.

The claims cover a specific antibody defined by its complementarity determining regions that bind filovirus glycoproteins broadly, methods utilizing this antibody for detecting filovirus in biological samples by various immunoassays, and methods of treating filovirus infection or preventing such infection by administering compositions comprising the antibody.

Stated Advantages

The antibody panel derived from ribosomal display is broadly cross-reactive to all known human pathogenic filoviruses, enabling pan-filovirus detection and identification.

The ribosome display method used to generate the antibodies is inexpensive, rapid, and produces high-affinity antibodies.

The antibodies recognize native conformational epitopes rather than denatured forms, allowing effective binding and detection of filovirus glycoproteins in their natural structure.

The broadly cross-reactive scFvs have potential diagnostic and therapeutic applications for filovirus infection.

Documented Applications

Detection of filovirus in biological samples using antibodies with specific CDRs by forming antibody:target complexes detected via ELISA, Western blot, or immunofluorescence assays.

Treatment or prophylaxis of subjects having or at risk of having filovirus infections by administering pharmaceutical compositions containing the antibodies.

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