IP Library › Granted Patent US 11,180,546
Granted Patent B2
US 11,180,546 · App. 15/999,368 · Granted Nov 23, 2021

TGFbeta 2 antibodies

Inventors: Chikwendu Ibebunjo (Newton, MA); Carsten Jacobi (Muttenz, CH); Angelika Meyer (Basel, CH); Eveline Schaadt (Oberhaching, DE); Anne-Ulrike Trendelenburg (Cambridge, MA); Olga Vladimirovna Mitina (Munich, DE)
Assignee: NOVARTIS AG
C07K16/22A61K2039/505C07K2317/14C07K2317/33C07K2317/34C07K2317/55C07K2317/565C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 11,180,546
App. No.
15/999,368
Granted
Nov 23, 2021
Kind
B2
Abstract

This invention is in the field of anti-transforming growth factor beta 2 (TGF-β2) antibodies. In particular, the invention provides human monoclonal antibodies that bind the human TGF-β2 isoform preferentially over the human TGF-β1 or TGF-β3 isoforms.

Claims (31)

1. A human monoclonal anti-transforming growth factor beta 2 (TGF-β2) TGF-β02 antibody or a functional fragment thereof that neutralizes the human TGF-β isoform TGF-β02 and does not neutralize human isoform TGF-β3, wherein neutralization is determined by a Smad dependent reporter gene assay, and wherein said antibody or functional fragment thereof comprises:

(a) a heavy chain variable region CDR1 of SEQ ID NO: 1; a heavy chain variable region CDR2 of SEQ ID NO: 2; a heavy chain variable region CDR3 of SEQ ID NO: 3; a light chain variable region CDR1 of SEQ ID NO: 11; a light chain variable region CDR2 of SEQ ID NO: 12; and a light chain variable region CDR3 of SEQ ID NO: 13,

(b) a heavy chain variable region CDR1 of SEQ ID NO: 21 a heavy chain variable region CDR2 of SEQ ID NO: 22; a heavy chain variable region CDR3 of SEQ ID NO: 23; a light chain variable region CDR1 of SEQ ID NO: 31; a light chain variable region CDR2 of SEQ ID NO: 32; and a light chain variable region CDR3 of SEQ ID NO: 33,

(c) a heavy chain variable region CDR1 of SEQ ID NO: 41; a heavy chain variable region CDR2 of SEQ ID NO: 42; a heavy chain variable region CDR3 of SEQ ID NO: 43; a light chain variable region CDR1 of SEQ ID NO: 51; a light chain variable region CDR2 of SEQ ID NO: 52; and a light chain variable region CDR3 of SEQ ID NO: 53,

(d) a heavy chain variable region CDR1 of SEQ ID NO: 61; a heavy chain variable region CDR2 of SEQ ID NO: 62; a heavy chain variable region CDR3 of SEQ ID NO: 63; a light chain variable region CDR1 of SEQ ID NO: 71; a light chain variable region CDR2 of SEQ ID NO: 72; and a light chain variable region CDR3 of SEQ ID NO: 73,

(e) a heavy chain variable region CDR1 of SEQ ID NO: 81; a heavy chain variable region CDR2 of SEQ ID NO: 82; a heavy chain variable region CDR3 of SEQ ID NO: 83; a light chain variable region CDR1 of SEQ ID NO: 91; a light chain variable region CDR2 of SEQ ID NO: 92; and a light chain variable region CDR3 of SEQ ID NO: 93, or

(f) a heavy chain variable region CDR1 of SEQ ID NO: 101; a heavy chain variable region CDR2 of SEQ ID NO: 102; a heavy chain variable region CDR3 of SEQ ID NO: 103; a light chain variable region CDR1 of SEQ ID NO: 111; a light chain variable region CDR2 of SEQ ID NO: 112; and a light chain variable region CDR3 of SEQ ID NO: 113.

2. The antibody or functional fragment according to claim 1 , wherein said antibody or functional fragment thereof comprises a VH polypeptide sequence having at least 95% sequence identity to at least one of SEQ ID NOs: 7, 27, 47, 67, 87, or 107 and a VL polypeptide sequence having at least 95% sequence identity to at least one of SEQ ID NOs: 17, 37, 57, 77, 97, or 117.

3. The antibody or functional fragment according to claim 1 , wherein said antibody or functional fragment thereof comprises a full length heavy chain amino acid sequence having at least 95% sequence identity to at least one sequence selected from the group consisting of SEQ ID NOs: 9, 29, 49, 69, 89, 109 and a full length light chain amino acid sequence having at least 95% sequence identity to at least one sequence selected from the group consisting of SEQ ID NOs: 19, 39, 59, 79, 99, 119.

4. The antibody or functional fragment according to claim 1 , which is a human monoclonal anti-TGF-β2 antibody, and which comprises:

(a) the variable heavy chain sequence of SEQ ID NO: 7 and variable light chain sequence of SEQ ID NO: 17;

(b) the variable heavy chain sequence of SEQ ID NO: 27 and variable light chain sequence of SEQ ID NO: 37;

(c) the variable heavy chain sequence of SEQ ID NO: 47 and variable light chain sequence of SEQ ID NO: 57;

(d) the variable heavy chain sequence of SEQ ID NO: 67 and variable light chain sequence of SEQ ID NO: 77;

(e) the variable heavy chain sequence of SEQ ID NO: 87 and variable light chain sequence of SEQ ID NO: 97; or

(f) the variable heavy chain sequence of SEQ ID NO: 107 and variable light chain sequence of SEQ ID NO: 117.

5. The antibody or functional fragment according to claim 1 , which is a human monoclonal anti-TGF-β2 antibody, and which comprises:

(a) the heavy chain sequence of SEQ ID NO: 9 and light chain sequence of SEQ ID NO: 19;

(b) the heavy chain sequence of SEQ ID NO: 29 and light chain sequence of SEQ ID NO: 39;

(c) the heavy chain sequence of SEQ ID NO: 49 and light chain sequence of SEQ ID NO: 59;

(d) the heavy chain sequence of SEQ ID NO: 69 and light chain sequence of SEQ ID NO: 79;

(e) the heavy chain sequence of SEQ ID NO: 89 and light chain sequence of SEQ ID NO: 99; or

(f) the heavy chain sequence of SEQ ID NO: 109 and light chain sequence of SEQ ID NO: 119.

6. An isolated polynucleotide sequence encoding an antibody or functional fragment according to claim 1 .

7. The isolated polynucleotide sequence according to claim 6 , comprising one or more of SEQ ID NOs: 8, 10, 18, 20, 28, 30, 38, 40, 48, 50, 58, 60, 68, 70, 78, 80, 88, 90, 98, 100, 108, 110, 118, or 120.

8. A cloning or expression vector comprising one or more isolated polynucleotide sequences according to claim 7 .

9. The vector according to claim 8 , wherein said vector comprises one or more of SEQ ID NOs: 8, 10, 18, 20, 28, 30, 38, 40, 48, 50, 58, 60, 68, 70, 78, 80, 88, 90, 98, 100, 108, 110, 118, or 120, or fragment thereof encoding at least one CDR region.

10. A host cell comprising one or more vectors according to claim 8 .

11. A process for the production of an anti-TGF-02 antibody or functional fragment thereof, comprising culturing the host cell of claim 10 and isolating said antibody or functional fragment.

12. A pharmaceutical composition comprising an antibody or functional fragment thereof according to claim 1 .

13. The pharmaceutical composition according to claim 12 , further comprising a pharmaceutically acceptable diluent or carrier.

Assignments (6)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 26, 2018
From: MEYER, ANGELIKA; JACOBI, CARSTEN
To: NOVARTIS PHARMA AG
Reel/Frame 047580/0614 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 26, 2018
From: NOVARTIS PHARMA AG
To: NOVARTIS AG
Reel/Frame 047580/0637 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 26, 2018
From: TRENDELENBURG, ANNE-ULRIKE; IBEBUNJO, CHIKWENDU
To: NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH, INC.
Reel/Frame 047580/0678 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 26, 2018
From: NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH, INC.
To: NOVARTIS AG
Reel/Frame 047580/0699 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 26, 2018
From: VLADIMIROVNA, OLGA; SCHAADT, EVELINE
To: MORPHOSYS AG
Reel/Frame 047580/0768 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 26, 2018
From: MORPHOSYS AG
To: NOVARTIS AG
Reel/Frame 047580/0861 →
Continuity (2)
Provisional Application 62296282 · Feb 17, 2016
Related Publication 20190092846A1 · Mar 28, 2019