Anti-respiratory syncytial virus antibodies, methods of their generation and use
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11725045-B2
Publication Date
2023-08-15
Expiration Date
Abstract
Provided are antibodies or antigen binding polypeptides characterized by the ability to neutralize respiratory syncytial virus (RSV). Specifically, the antibodies or antigen binding polypeptides are characterized by high affinity binding to RSV fusion glycoprotein (RSVF). Further provided are methods for their identification, isolation, generation, preparation, and use, as well as the heavy chain and light chain sequences of the antibodies provided.
Core Innovation
The document discloses anti-RSV fusion (F) antibodies, including antibodies that specifically bind to RSV F and neutralize RSV F. It provides extensive amino-acid sequence information for anti-RSV F antibodies, including heavy- and light-chain variable regions associated with antibody numbers, and includes exemplary embodiments with specified CDR sequence identity thresholds linked to defined antibody numbers and tables. The antibodies are described with targeting of RSV prefusion F (preF) and/or postfusion F (postF), and with defined epitope(s) on prefusion F.
The document describes antibodies that cross-compete or bind the same RSV F epitope(s), including binding preferences for preF versus postF. Competition relationships are described relative to specific antibody numbers, and the embodiments include neutralization potency (IC50 ranges) and binding affinity (KD by SPR). The description further characterizes antibody-epitope interaction features using interaction residues/loops and CDR region involvement, including specific residues in CDRs and interactions involving prefusion F loops.
In addition to the antibody sequences and binding/competition characterization, the document discloses nucleic acids encoding the antibodies, expression constructs, host cells, and pharmaceutical compositions containing the antibodies. Methods for preventing and treating RSV infection and for detecting RSV are included. The antibody embodiments include considerations of polyreactivity profiles and, in some embodiments, Fc region modification using Fc variants.
The disclosed work characterizes human RSV F-specific infant and naive B cell antibody repertoires, with focus on age-dependent epitope targeting across RSV F conformations. It reports that antibodies targeting preF-preferred antigenic site III dominate in infants less than 3 months, while antibodies targeting site I preferentially bind postF and are often non-neutralizing. The document also characterizes specific site I and site III antibodies using structural and binding analyses, including ADI-14359 and ADI-19425, and includes an additional example comparing mucosal and systemic RSV F-specific memory B cell responses in adenoid compartment versus peripheral blood mononuclear cells.
Claims Coverage
The provided claim set includes independent claim coverage for two RSV F-neutralizing antibody components defined by heavy- and light-chain CDRs, with no additional antibodies included.
CdRs matching antibody number 843 plus second antibody from defined set
A composition comprising an antibody component consisting of a first antibody or antigen-binding fragment whose heavy- and light-chain CDRs are found in antibody number 843, and a second antibody or antigen-binding fragment whose heavy- and light-chain CDRs are found in an antibody selected from the specified group of antibody numbers.
Specifically binds and neutralizes RSV F
Each of the first and second antibodies or antigen-binding fragments specifically binds to and neutralizes RSV F.
No additional antibodies included
The composition does not include any antibodies other than the antibody component.
Overall, the claims define an antibody-only composition containing two RSV F-neutralizing antibodies or fragments selected by heavy- and light-chain CDR identity to antibody number 843 and to a specified set of antibody numbers, with explicit exclusion of any additional antibodies.
Stated Advantages
Provides therapeutic, prophylactic, and diagnostic uses for the described RSV F-specific neutralizing antibodies and antigen-binding fragments.
Documented Applications
Therapeutic and prophylactic use for treating RSV infection, based on administration of the claimed composition to a mammal, including human.
Diagnostic uses are described for the disclosed antibodies and antigen-binding fragments.
Interested in licensing this patent?