IP Library › Granted Patent US 11,932,681
Granted Patent B2
US 11,932,681 · App. 17/059,934 · Granted Mar 19, 2024

Hepatitis B antibodies

Inventors: Stefan Ewert (Geroldswil, CH); Meghan Marie Holdorf (Oakland, CA); Elisabetta Traggiai (Basel, CH)
Assignee: Novartis AG
C07K16/082A61K2039/505C07K2317/21C07K2317/33C07K2317/55C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 11,932,681
App. No.
17/059,934
Granted
Mar 19, 2024
Kind
B2
Abstract

The present invention relates to anti-HBsAg antibodies, antibody fragments, and their uses for the prevention and treatment of hepatitis B virus infection and associated diseases.

Claims (51)

1. An isolated antibody, wherein said antibody or antigen binding fragment thereof comprises:

(i) a heavy chain variable region that comprises (a) a HCDR1 (CDR-Complementarity Determining Region) of SEQ ID NO: 9, (b) a HCDR2 of SEQ ID NO:10, (c) a HCDR3 of SEQ ID NO:11 and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:25, (e) a LCDR2 of SEQ ID NO:26, and (f) a LCDR3 of SEQ ID NO:27;

(ii) a heavy chain variable region that comprises (a) a HCDR1 of SEQ ID NO:41, (b) a HCDR2 of SEQ ID NO:42, (c) a HCDR3 of SEQ ID NO:43; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:57, (e) a LCDR2 of SEQ ID NO:58, and (f) a LCDR3 of SEQ ID NO:59;

(iii) a heavy chain variable region that comprises (a) a HCDR1 of SEQ ID NO:73, (b) a HCDR2 of SEQ ID NO:74, (c) a HCDR3 of SEQ ID NO:75; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:89, (e) a LCDR2 of SEQ ID NO:90, and (f) a LCDR3 of SEQ ID NO:91;

(iv) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO:105, (b) a HCDR2 of SEQ ID NO:106, (c) a HCDR3 of SEQ ID NO:107; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:121, (e) a LCDR2 of SEQ ID NO:122, and (f) a LCDR3 of SEQ ID NO:123;

(v) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO:137, (b) a HCDR2 of SEQ ID NO:138, (c) a HCDR3 of SEQ ID NO:139; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:153, (e) a LCDR2 of SEQ ID NO:154, and (f) a LCDR3 of SEQ ID NO:155;

(vi) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO:169, (b) a HCDR2 of SEQ ID NO:170, (c) a HCDR3 of SEQ ID NO:171; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:185, (e) a LCDR2 of SEQ ID NO:186, and (f) a LCDR3 of SEQ ID NO:187;

(vii) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO:201, (b) a HCDR2 of SEQ ID NO: 202, (c) a HCDR3 of SEQ ID NO:203; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:217, (e) a LCDR2 of SEQ ID NO:218, and (f) a LCDR3 of SEQ ID NO:219;

(viii) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO:233, (b) a HCDR2 of SEQ ID NO:234, (c) a HCDR3 of SEQ ID NO:235; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:249, (e) a LCDR2 of SEQ ID NO:250, and (f) a LCDR3 of SEQ ID NO:251;

(ix) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO:265, (b) a HCDR2 of SEQ ID NO: 266, (c) a HCDR3 of SEQ ID NO:267; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:281, (e) a LCDR2 of SEQ ID NO:282, and (f) a LCDR3 of SEQ ID NO: 283;

(x) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO:297, (b) a HCDR2 of SEQ ID NO: 298, (c) a HCDR3 of SEQ ID NO:299; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:313, (e) a LCDR2 of SEQ ID NO:314, and (f) a LCDR3 of SEQ ID NO: 315;

(xi) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO:329, (b) a HCDR2 of SEQ ID NO:330, (c) a HCDR3 of SEQ ID NO:331; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:345, (e) a LCDR2 of SEQ ID NO:346, and (f) a LCDR3 of SEQ ID NO: 347;

(xii) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO:361, (b) a HCDR2 of SEQ ID NO:362, (c) a HCDR3 of SEQ ID NO:363; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:377, (e) a LCDR2 of SEQ ID NO:378, and (f) a LCDR3 of SEQ ID NO: 379;

(xiii) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO:393, (b) a HCDR2 of SEQ ID NO:394, (c) a HCDR3 of SEQ ID NO:395; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:409, (e) a LCDR2 of SEQ ID NO:410, and (f) a LCDR3 of SEQ ID NO:411;

(xiv) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO:425, (b) a HCDR2 of SEQ ID NO:426, (c) a HCDR3 of SEQ ID NO:427; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:441, (e) a LCDR2 of SEQ ID NO:442, and (f) a LCDR3 of SEQ ID NO: 443;

(xv) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO:457, (b) a HCDR2 of SEQ ID NO:458, (c) a HCDR3 of SEQ ID NO:459; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:473, (e) a LCDR2 of SEQ ID NO:474, and (f) a LCDR3 of SEQ ID NO:475; or

(xvi) a heavy chain variable region that comprises: (a) a HCDR1 of SEQ ID NO:489, (b) a HCDR2 of SEQ ID NO:490, (c) a HCDR3 of SEQ ID NO:491; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:505, (e) a LCDR2 of SEQ ID NO:506, and (f) a LCDR3 of SEQ ID NO: 507.

2. The antibody of claim 1 , wherein one or two amino acids within a CDR have been modified, deleted or substituted.

3. The antibody of claim 1 , that retains at least 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% identity over either the variable heavy chain region or the variable light chain region.

4. The antibody of claim 1 , wherein the antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, a human engineered antibody, a human antibody, a single chain antibody (scFv) or an antibody fragment.

5. An isolated antibody or antigen binding fragment thereof, wherein said antibody or antigen binding fragment thereof comprises:

(i) a heavy chain variable region (vH) that comprises SEQ ID NO:18, and a light chain variable region (vL) that comprises SEQ ID NO: 34;

(ii) a heavy chain variable region (vH) that comprises SEQ ID NO: 50, and a light chain variable region (vL) that comprises SEQ ID NO: 66;

(iii) a heavy chain variable region (vH) that comprises SEQ ID NO: 82, and a light chain variable region (vL) that comprises SEQ ID NO:98;

(iv) a heavy chain variable region (vH) that comprises SEQ ID NO:114, and a light chain variable region (vL) that comprises SEQ ID NO:130;

(v) a heavy chain variable region (vH) that comprises SEQ ID NO:146, and a light chain variable region (vL) that comprises SEQ ID NO:162;

(vi) a heavy chain variable region (vH) that comprises SEQ ID NO:178, and a light chain variable region (vL) that comprises SEQ ID NO:194;

(vii) a heavy chain variable region (vH) that comprises SEQ ID NO:210, and a light chain variable region (vL) that comprises SEQ ID NO:226;

(viii) a heavy chain variable region (vH) that comprises SEQ ID NO:242, and a light chain variable region (vL) that comprises SEQ ID NO:258;

(ix) a heavy chain variable region (vH) that comprises SEQ ID NO:274, and a light chain variable region (vL) that comprises SEQ ID NO:290;

(x) a heavy chain variable region (vH) that comprises SEQ ID NO:306, and a light chain variable region (vL) that comprises SEQ ID NO:322;

(xi) a heavy chain variable region (vH) that comprises SEQ ID NO:338, and a light chain variable region (vL) that comprises SEQ ID NO:354;

(xii) a heavy chain variable region (vH) that comprises SEQ ID NO:370, and a light chain variable region (vL) that comprises SEQ ID NO:386;

(xiii) a heavy chain variable region (vH) that comprises SEQ ID NO:402, and a light chain variable region (vL) that comprises SEQ ID NO:418;

(xiv) a heavy chain variable region (vH) that comprises SEQ ID NO:434, and a light chain variable region (vL) that comprises SEQ ID NO:450;

(xv) a heavy chain variable region (vH) that comprises SEQ ID NO:466, and a light chain variable region (vL) that comprises SEQ ID NO:482; or

(xvi) a heavy chain variable region (vH) that comprises SEQ ID NO:498, and a light chain variable region (vL) that comprises SEQ ID NO:514.

6. The antibody or fragment thereof of claim 5 , that retains at least 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99% identity over either the variable light or variable heavy region.

7. The antibody of claim 5 , wherein one, two, three, four or five, but less than 10 amino acids within the variable light or variable heavy region have been modified, deleted or substituted.

8. The antibody of claim 5 , wherein the antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, a human engineered antibody, a human antibody, a single chain antibody (scFv) or an antibody fragment.

9. The antibody of claim 1 wherein the antibody or fragment thereof has reduced glycosylation or no glycosylation or is hypofucosylated.

10. A pharmaceutical composition comprising the antibody or fragment thereof, of claim 1 , further comprising a pharmaceutically acceptable carrier.

11. A pharmaceutical composition comprising a plurality of an antibody or antigen binding fragment of claim 1 , wherein at least 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 5% or more or more of the antibodies in the composition have an α2,3-linked sialic acid residue.

12. A pharmaceutical composition comprising a plurality of an antibody or antigen binding fragment of claim 1 , wherein none of the antibodies comprise a bisecting GlcNAc.

13. The pharmaceutical composition comprising the antibody or fragment thereof of claim 1 , wherein the composition is prepared as a lyophilisate.

14. A method of neutralizing a hepatitis B virus infection comprising administering via injection or infusion to a patient in need an effective amount of the antibody of claim 1 .

15. A method of treating or reducing the likelihood of hepatitis B virus associated disorder, comprising administering via injection or infusion to a patient in need an effective amount of the antibody of claim 1 , and wherein the disorder is: liver failure, cirrhosis, or hepatocellular carcinoma.

16. A nucleic acid that encodes the antibody or antigen binding fragment of claim 1 .

17. A vector comprising the nucleic acid of claim 16 .

18. A host cell comprising the vector of claim 17 .

19. A diagnostic reagent comprising the antibody or antigen binding fragment thereof of claim 1 which is labeled.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 7, 2020
From: HOLDORF, MEGHAN MARIE
To: NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH, INC.
Reel/Frame 054568/0167 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 7, 2020
From: NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH, INC.
To: NOVARTIS AG
Reel/Frame 054568/0376 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 7, 2020
From: EWERT, STEFAN; TRAGGIAI, ELISABETTA
To: NOVARTIS PHARMA AG
Reel/Frame 054568/0627 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 7, 2020
From: NOVARTIS PHARMA AG
To: NOVARTIS AG
Reel/Frame 054568/0719 →
Continuity (2)
Provisional Application 62678756 · May 31, 2018
Related Publication 20210221871A1 · Jul 22, 2021
Cited By (1)
US 12,331,104