IP Library Granted Patent US 11,965,032
Granted Patent B1
US 11,965,032 · App. 18/167,631 · Granted Apr 23, 2024

Anti-CD20 antibody compositions

Inventors: George Costas Avgerinos (Sudbury, MA); Patrick Michael Hossler (Westborough, MA); Jill A. Myers (Brookline, MA); Yune Z. Kunes (Cambridge, MA)
Assignees: TG Therapeutics, Inc.; Laboratoire Francais du Fractionnement et des Biotechnologies
C07K16/2887A61K2039/505C07K2317/41C07K2317/732C07K2317/734C07K2317/92
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Quick Facts
Patent No.
US 11,965,032
App. No.
18/167,631
Granted
Apr 23, 2024
Kind
B1
Abstract

Provided herein are populations of anti-CD20 antibody proteins with specified ranges of post-translational modifications. Also provided are methods of using and methods of making such populations of anti-CD20 antibody proteins.

Claims (82)

1. A single batch preparation of a population of anti-CD20 antibody proteins, wherein the anti-CD20 antibody proteins in the population are expressed from one or more nucleic acid sequences encoding a heavy chain comprising the amino acid sequence of SEQ ID NO:1 and a light chain comprising the amino acid sequence of SEQ ID NO:2, wherein the population of anti-CD20 antibody proteins has an N-glycan profile comprising 10 to 20% galactosylated glycans and 20 to 40% fucosylated glycans, and wherein the population of anti-CD20 antibody proteins is produced in a 15,000 L or 20,000 L bioreactor.

2. The single batch preparation of claim 1 , wherein the N-glycan profile comprises 23% to 36% fucosylated glycans.

3. The single batch preparation of claim 1 , wherein the N-glycan profile comprises 27% to 37% fucosylated glycans.

4. The single batch preparation claim 1 , wherein the N-glycan profile comprises 16 to 18% galactosylated glycans.

5. The single batch preparation of claim 1 , wherein the N-glycan profile comprises 15% to 19% galactosylated glycans.

6. The single batch preparation of claim 1 , wherein the N-glycan profile comprises 12% to 30% bisecting N-glycans.

7. The single batch preparation of claim 1 , wherein the N-glycan profile comprises 16% to 20% bisecting N-glycans.

8. The single batch preparation of claim 6 , wherein the bisecting N-glycans comprise one or more of G0B, G0FB, G1FB, G2FBS1, and G2FBS2.

9. The single batch preparation of claim 1 , wherein the population of anti-CD20 antibody proteins further comprises at least two N-glycans within the following relative abundance ranges:

(a) 0.3% to 2% G0-GN;

(b) 0.1% to 2% G0F-GN;

(c) 30% to 60% G0;

(d) 0.1% to 1% G1-GN;

(e) 5% to 20% G0B;

(f) 5% to 30% G0F;

(g) 0.1% to 1.5% Man5;

(h) 1% to 15% G0FB;

(i) 1% to 13% G1;

(j) 0.5% to 10% G1′;

(k) 0.5% to 6% G1B;

(l) 0.5% to 12% G1F;

(m) 0.1% to 3% G1F′;

(n) 0.1% to 3% G1FB;

(o) 0.1% to 2% G2; and

(p) 0.1% to 2% G2F.

10. The single batch preparation of claim 9 , wherein the population of anti-CD20 antibody proteins further comprises at least two N-glycans within the following relative abundance range:

(a) 0.8% to 1.1% G0-GN;

(b) 0.5% to 1.1% G0F-GN;

(c) 42.5% to 48.8% G0;

(d) 0.3% to 0.6% G1-GN;

(e) 9.5% to 14.1% G0B;

(f) 12.8% to 19.7% G0F;

(g) 0.4% to 0.7% Man5;

(h) 5.1% to 7.0% G0FB;

(i) 5.7% to 6.4% G1;

(j) 2.7% to 3.3% G1′;

(k) 1.4% to 2.0% G1B;

(l) 2.6% to 4.2% G1F;

(m) 1.1% to 1.6% G1F′;

(n) 1.1% to 1.8% G1FB;

(o) 0.5% to 0.7% G2; and

(p) 0.3% to 0.5% G2F.

11. The single batch preparation of claim 9 , wherein the population of anti-CD20 antibody proteins further comprises at least two N-glycans in the following relative abundance:

(a) 0.9% G0-GN;

(b) 0.8% G0F-GN;

(c) 46.1% G0;

(d) 0.5% G1-GN;

(e) 10.9% G0B;

(f) 17.0% G0F;

(g) 0.6% Man5;

(h) 6.0% G0FB;

(i) 6.1% G1;

(j) 2.9% G1′;

(k) 1.6% G1B;

(l) 3.2% G1F;

(m) 1.3% G1F′;

(n) 1.3/o G1FB;

(o) 0.5% G2; and

(p) 0.3% G2F.

12. The single batch preparation of claim 9 , wherein the population of anti-CD20 antibody proteins further comprises at least three, four or five N-glycans within the following relative abundance ranges:

(a) 0.3% to 2% G0-GN;

(b) 0.1% to 2% G0F-GN;

(c) 30% to 60% G0;

(d) 0.1% to 1% G1-GN;

(e) 5% to 20% G0B;

(f) 5% to 30% G0F;

(g) 0.1% to 1.5% Man5;

(h) 1% to 15% G0FB;

(i) 1% to 13% G1;

(j) 0.5% to 10% G1′;

(k) 0.5% to 6% G1B;

(l) 0.5% to 12% G1F;

(m) 0.1% to 3% G1F′;

(n) 0.1% to 3% G1FB;

(o) 0.1% to 2% G2; and

(p) 0.1% to 2% G2F.

13. The single batch preparation of claim 1 , wherein less than 10% of the anti-CD20 antibody proteins in the population is non-glycosylated.

14. The single batch preparation of claim 13 , wherein less than 5% of the anti-CD20 antibody proteins in the population is non-glycosylated.

15. The single batch preparation of claim 13 , wherein less than 1% of the anti-CD20 antibody proteins in the population is non-glycosylated.

16. The single batch preparation of claim 1 , wherein the single batch comprises at least 100 g of the anti-CD20 antibody proteins.

17. The single batch preparation of claim 1 , wherein the single batch comprises at least 120 g of the anti-CD20 antibody proteins.

18. The single batch preparation of claim 1 , wherein the single batch comprises at least 150 g of the anti-CD20 antibody proteins.

Assignments (3)
SECURITY INTEREST Recorded Oct 3, 2024
From: TG THERAPEUTICS, INC.
To: BLUE OWL CAPITAL CORPORATION
Reel/Frame 068787/0338 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 2, 2023
From: TG THERAPEUTICS, INC.
To: LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES BIOTECHNOLOGIES
Reel/Frame 064466/0193 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 30, 2023
From: AVGERINOS, GEORGE COSTAS; HOSSLER, PATRICK MICHAEL; MYERS, JILL A.; KUNES, YUNE Z.
To: TG THERAPEUTICS, INC.
Reel/Frame 063800/0678 →
Continuity (1)
Provisional Application 63347852 · Jun 1, 2022