Therapy for filovirus infection
Inventors
Lai, Jonathan R. • Koellhoffer, Jayne F. • Frei, Julia • Chandran, Kartik • Sidhu, Sachdev • Chen, Gang • Dye, John M. • Zak, Samantha
Assignees
University of Toronto • Albert Einstein College of Medicine • United States Department of the Army
Publication Number
US-10435461-B2
Publication Date
2019-10-08
Expiration Date
2035-08-06
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Abstract
The present invention addresses a need for improved treatments for filovirus infections. This invention provides an isolated humanized anti-filovirus glycoprotein pre-fusion core antibody comprising a framework region having a sequence of 95% or greater identity to a human antibody framework region. Also provided is a method of treating and/or inhibiting a filovirus infection in a subject comprising administering to the subject an amount of any of the antibodies described herein, or an amount of an antigen-binding fragment thereof. Also provided is composition comprising any of the antibodies described herein, or or an amount of an antigen-binding fragment thereof. In an embodiment, the composition comprises a pharmaceutically acceptably carrier.
Core Innovation
The invention provides an isolated humanized anti-filovirus glycoprotein pre-fusion core antibody that has a framework region with at least 95% identity to a human antibody framework region. The antibody comprises specific heavy chain complementarity determining regions (CDRs) including CDR1, CDR2, and CDR3 sequences, as well as a light chain sequence with defined CDRs, particularly a light chain CDR3 comprising a specific amino acid sequence. Antigen-binding fragments of these antibodies and compositions containing these antibodies or fragments, optionally with pharmaceutically acceptable carriers, are also provided.
The invention includes methods of treating or inhibiting filovirus infection in a subject by administering an effective amount of the described antibodies, antigen-binding fragments, or compositions. These methods cover both prophylactic administration prior to virus exposure and therapeutic administration post-exposure. The filoviruses targeted include Ebola viruses such as the Sudan strain, as well as Marburg viruses, with embodiments involving neutralizing antibodies targeting the prefusion core of the glycoprotein spike.
Claims Coverage
The patent includes one principal independent claim directed to a humanized antibody and related claims covering antigen-binding fragments, compositions, and therapeutic methods. The inventive features focus on the antibody's specific sequences and its use in treating filovirus infections.
Humanized antibody with defined CDR sequences
An isolated humanized anti-Sudan strain Ebola virus glycoprotein pre-fusion core antibody comprising a framework region with 95% or greater identity to a human antibody framework region, including a heavy chain CDR3 sequence of QLYGNSFFDY, heavy chain CDR1 sequence of GFAFNYYDMF, heavy chain CDR2 of YIKPGGGNTYYADSV, and a light chain containing CDR1, CDR2, and a specific light chain CDR3 comprising CQQHYSTPLT, along with defined framework sequences.
Antigen-binding fragments of the humanized antibody
Provision of antigen-binding fragments derived from the humanized antibody, which retain the specified binding characteristics to the filovirus glycoprotein pre-fusion core.
Compositions comprising the humanized antibody or fragments
Pharmaceutical compositions comprising the humanized antibody or its antigen-binding fragments, optionally including pharmaceutically acceptable carriers suitable for administration.
Methods of treating or inhibiting filovirus infection
Methods involving administering an effective amount of the humanized antibody, antigen-binding fragment, or composition to a subject to treat or inhibit filovirus infection, specifically infections by the Sudan strain of Ebola virus, including both pre- and post-exposure administration.
Neutralizing activity and specific sequence embodiments
The antibody is a neutralizing antibody targeting the filovirus glycoprotein prefusion core. The heavy and light chain sequences can include specific embodiments detailed by certain SEQ ID NOs, confirming the defined sequence identity and activity.
The claims cover humanized antibodies with specific heavy and light chain CDR sequences targeting the filovirus glycoprotein prefusion core, corresponding antigen-binding fragments, pharmaceutical compositions containing them, and methods of treating or preventing filovirus infections including the Sudan strain of Ebola virus.
Stated Advantages
The antibody-based therapy provides improved treatments for filovirus infections, offering prophylactic and therapeutic potential.
Humanized antibodies with optimized sequences enhance neutralization potency, potentially improving protection compared to prior murine antibodies.
Antibody treatments have lower barriers to regulatory approval relative to other therapeutic platforms and allow for post-exposure administration.
Documented Applications
Treatment and prophylaxis of filovirus infections in subjects, including post-exposure and pre-exposure scenarios.
Use in compositions comprising pharmaceutically acceptable carriers for administration to subjects infected with or exposed to filoviruses, including Sudan strain Ebola virus and Marburg virus.
Use as diagnostic kits to detect filovirus presence using the described antibodies.
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