US 12,747,283 B2Granted

Compositions and methods related to human neutralizing antibodies to hepatitis B

AssigneeThe Rockefeller University

InventorsQiao Wang, Michel Nussenzweig

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Abstract

Provided are broadly neutralizing antibodies (bNAbs) and antigen binding fragments thereof that bind with specificity to epitopes expressed by Hepatitis B vims (HBV). The bNAbs target non-overlapping epitopes on the HBV S antigen (HBsAg). Pharmaceutical compositions that contain the bNAbs, or modified bNAbs, are provided. Combinations of the bNAbs are included, and are useful for prophylaxis and therapy of HBV infection, and for inhibiting development of HBV escape mutations in infected individuals. Expression vectors encoding the bNAbs and antigenic fragments of them are included, as are methods of making the bNAbs and antigenic fragments of them. HBV peptides for use as vaccines are provided, and include at least two non-overlapping epitopes from the HBsAg. Diagnostic reagents comprising the bNAbs or antigenic fragments thereof are provided, as are methods of detecting HBV and diagnosing HBV infection.

Claims12

Dependent claims

A combination of recombinant or isolated antibodies or antigen binding fragments thereof, said combination comprising a first antibody (H019) comprising a heavy chain variable region that is IGHV4-30-4*01;

a heavy chain diverse region that is IGHD2-2*03;
a heavy chain joining region that is IGHJ3*02, a heavy chain CDR1 that comprises the sequence GGSITTGDYY (SEQ ID NO:
18), a heavy chain CDR2 that comprises the sequence IYYSGST (SEQ ID NO:
19), and a heavy chain CDR3 that comprises the sequence AIYMDEAWAFE (SEQ ID NO:
20);
and a kappa light chain variable region that is IGKV1-39*01, a kappa light chain joining region that is IGKJ2*01, a light chain CDR1 that comprises the sequence QSVGNY (SEQ ID NO:
21), a light chain CDR2 that is AVS, and a light chain CDR3 that comprises the sequence QQSYTISLFT (SEQ ID NO:
22);
and
a second antibody (H017) comprising a heavy chain variable region that is IGHV3-74*01, a heavy chain diverse region that is IGHD3-10*01, a heavy chain joining region that is IGHJ4*02, a heavy chain CDR1 that comprises the sequence GFTFSNYW (SEQ ID NO:
13), a heavy chain CDR2 that comprises the sequence ISTDGSST (SEQ ID NO:
14), and a heavy chain CDR3 that comprises the sequence ARGSTYYFGSGSVDY (SEQ ID NO:
15);
and a lambda light chain variable region that is IGLV2-14*01, a lambda light chain joining region that is IGLJ1*01, a light chain CDR1 that comprises the sequence SSDIGVYNY (SEQ ID NO:
16), a light chain CDR2 that is DVT, and a light chain CDR3 that comprises the sequence SSYRGSSTPYV (SEQ ID NO:
17).

13 more elements

A method for prophylaxis or therapy of a Hepatitis B virus infection comprising administering to an individual in need thereof an effective amount a combination of antibodies or antigen binding fragments thereof, wherein optionally least one antibody in the combination comprises at least one modification of its constant region, and wherein said combination comprises a first antibody (H019) comprising a heavy chain variable region that is IGHV4-30-4*01;

a heavy chain diverse region that is IGHD2-2*03;
a heavy chain joining region that is IGHJ3*02, a heavy chain CDR1 that comprises the sequence GGSITTGDYY (SEQ ID NO:
18), a heavy chain CDR2 that comprises the sequence IYYSGST (SEQ ID NO:
19), and a heavy chain CDR3 that comprises the sequence AIYMDEAWAFE (SEQ ID NO:
20);
and a kappa light chain variable region that is IGKV1-39*01, a kappa light chain joining region that is IGKJ2*01, a light chain CDR1 that comprises the sequence QSVGNY (SEQ ID NO:
21), a light chain CDR2 that is AVS, and a light chain CDR3 that comprises the sequence QQSYTISLFT (SEQ ID NO:
22);
and
a second antibody (H017) comprising a heavy chain variable region that is IGHV3-74*01, a heavy chain diverse region that is IGHD3-10*01, a heavy chain joining region that is IGHJ4*02, a heavy chain CDR1 that comprises the sequence GFTFSNYW (SEQ ID NO:
13), a heavy chain CDR2 that comprises the sequence ISTDGSST (SEQ ID NO:
14), and a heavy chain CDR3 that comprises the sequence ARGSTYYFGSGSVDY (SEQ ID NO:
15);
and a lambda light chain variable region that is IGLV2-14*01, a lambda light chain joining region that is IGLJ1*01, a light chain CDR1 that comprises the sequence SSDIGVYNY (SEQ ID NO:
16), a light chain CDR2 that is DVT, and a light chain CDR3 that comprises the sequence SSYRGSSTPYV (SEQ ID NO:
17).

13 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/641,396Filed 11 Sep 2020 · us provisional application
Priority: 11 Sep 2019
Published: US 2022/0315645 A16 Oct 2022
Granted: 29 Sep 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07K 16/082
DNA viruses: hepadnaviridae , e.g. hepatitis B virus
A61P 31/20
Antivirals: for DNA viruses
C07K 2317/33
Characterized by aspects of specificity or valency: crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
C07K 2317/34
Characterized by aspects of specificity or valency: identification of a linear epitope shorter than 20 amino acid residues or of a conformational…