IP Library › Granted Patent US 10,874,713

Granted Patent B2

US 10,874,713 · App. 15/542,466 · Granted Dec 29, 2020

Combined preparations for the treatment of cancer or infection

Inventors: Frederic Triebel (Versailles, FR); Chrystelle Brignone (Chatenay-Malabry, FR)

Assignee: IMMUTEP S.A.S.

A61K38/1774 A61K38/177 A61K39/3955 A61P31/16 A61P31/22 A61P35/04 C07K16/2818 A61K39/39558 A61K2300/00 C07K2317/70 C07K2317/76 C07K2319/30 C07K2319/32 Y02A50/30

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Quick Facts

Patent No.: US 10,874,713
App. No.: 15/542,466
Granted: Dec 29, 2020
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

Combined preparations, and pharmaceutical compositions, comprising: (a) LAG-3 protein, or a derivative thereof that is able to bind to MHC class II molecules; and (b) a programmed cell death protein-1 (PD-1) pathway inhibitor, are described. The PD-1 pathway inhibitor, such as an anti-PD-1 antibody or an anti-PD-L1 antibody, and a soluble derivative of LAG-3, acting as an APC activator, together synergistically activate T cells (in particular, CD8 + T cells). Use of the combined preparations and compositions as medicaments, in particular for the treatment of cancer or infection, and to methods for the treatment of cancer or infection, is described.

Claims (347)

1. A combined preparation comprising:

(a) a soluble LAG-3 protein, or a derivative of LAG-3 protein that is able to bind to MHC class II molecules, wherein the derivative of LAG-3 protein comprises recombinant soluble human LAG-3Ig fusion protein IMP321, wherein the soluble LAG-3 protein or the derivative of LAG-3 protein binds to MHC class II molecules on antigen-presenting cells (APCs), thereby activating APCs and further activating T cells; and

(b) a programmed cell death protein-1 (PD-1) pathway inhibitor, wherein the PD-1 pathway inhibitor is selected from the group consisting of pembrolizumab and nivolumab.

2. The combined preparation according to claim 1 , for co-administration or sequential administration of the soluble LAG-3 protein or the derivative of LAG-3 protein, and the PD-1 pathway inhibitor.

3. The combined preparation of claim 1 , wherein the soluble LAG-3 protein, or the derivative of LAG-3 protein, is separate from the PD-1 pathway inhibitor.

4. The combined preparation of claim 1 , wherein the soluble LAG-3 protein or the derivative of LAG-3 protein, is present at a unit dosage which is a molar equivalent of 0.25-30 mg of LAG-3Ig fusion protein IMP321.

5. The combined preparation of claim 1 , wherein the soluble LAG-3 protein, or the derivative of LAG-3 protein, is present in the combined preparation as a plurality of unit dosages and/or the PD-1 pathway inhibitor is present in the combined preparation as a plurality of unit dosages.

6. The combined preparation of claim 1 , wherein the PD-1 pathway inhibitor is present at a dose that is up to 50%, 1-50%, 1-25%, or 1-10%, of a typically prescribed dose of the PD-1 pathway inhibitor as a monotherapy, or wherein the PD-1 pathway inhibitor is present at a dose that is 0.1-50%, 0.1-25%, 0.1-20%, 0.1-10%, <20%, <10%, 0.1-<20%, 0.1-<10%, 0.01-<20%, or 0.01-<10% of a typically prescribed dose of the PD-1 pathway inhibitor as a monotherapy.

7. The combined preparation of claim 1 , wherein the soluble LAG-3 protein or the derivative of LAG-3 protein, and the PD-1 pathway inhibitor, are present in any of the combinations of dosage amounts shown in the Table below:

Human dose of LAG-3

protein or the derivative

of LAG-3 protein

Type of

Human dose of

(given as a mg dose of

PD-1 pathway

IMP321, or a molar

inhibitor

inhibitor:

equivalent thereof)

Pembrolizumab

0.07-350 mg

0.25-30 mg

0.07-175 mg

0.25-30 mg

0.07-70 mg

0.25-30 mg

0.07-<70 mg

0.25-30 mg

0.07-35 mg

0.25-30 mg

0.07-7 mg

0.25-30 mg

0.14-350 mg

0.25-30 mg

0.14-175 mg

0.25-30 mg

0.14-70 mg

0.25-30 mg

0.14-<70 mg

0.25-30 mg

0.14-35 mg

0.25-30 mg

0.14-7 mg

0.25-30 mg

Pembrolizumab

0.07-350 mg

1-30 mg

0.07-175 mg

1-30 mg

0.07-70 mg

1-30 mg

0.07-<70 mg

1-30 mg

0.07-35 mg

1-30 mg

0.07-7 mg

1-30 mg

0.14-350 mg

1-30 mg

0.14-175 mg

1-30 mg

0.14-70 mg

1-30 mg

0.14-70 mg

1-30 mg

0.14-<70 mg

1-30 mg

0.14-35 mg

1-30 mg

Pembrolizumab

0.07-350 mg

6-30 mg

0.07-175 mg

6-30 mg

0.07-70 mg

6-30 mg

0.07-<70 mg

6-30 mg

0.07-35 mg

6-30 mg

0.07-7 mg

6-30 mg

0.14-350 mg

6-30 mg

0.14-175 mg

6-30 mg

0.14-70 mg

6-30 mg

0.14-<70 mg

6-30 mg

0.14-35 mg

6-30 mg

0.14-7 mg

6-30 mg

Nivolumab

0.07-350 mg

0.25-30 mg

0.07-175 mg

0.25-30 mg

0.07-70 mg

0.25-30 mg

0.07-<70 mg

0.25-30 mg

0.07-35 mg

0.25-30 mg

0.07-7 mg

0.25-30 mg

0.14-350 mg

0.25-30 mg

0.14-175 mg

0.25-30 mg

0.14-70 mg

0.25-30 mg

0.14-<70 mg

0.25-30 mg

0.14-35 mg

0.25-30 mg

0.14-7 mg

0.25-30 mg

Nivolumab

0.07-350 mg

1-30 mg

0.07-175 mg

1-30 mg

0.07-70 mg

1-30 mg

0.07-<70 mg

1-30 mg

0.07-35 mg

1-30 mg

0.07-7 mg

1-30 mg

0.14-350 mg

1-30 mg

0.14-175 mg

1-30 mg

0.14-70 mg

1-30 mg

0.14-<70 mg

1-30 mg

0.14-35 mg

1-30 mg

0.14-7 mg

1-30 mg

Nivolumab

0.07-350 mg

6-30 mg

0.07-175 mg

6-30 mg

0.07-70 mg

6-30 mg

0.07-<70 mg

6-30 mg

0.07-35 mg

6-30 mg

0.07-7 mg

6-30 mg

0.14-350 mg

6-30 mg

0.14-175 mg

6-30 mg

0.14-70 mg

6-30 mg

0.14-<70 mg

6-30 mg

0.14-35 mg

6-30 mg

0.14-7 mg

6-30 mg.

8. The combined preparation of claim 1 , wherein the soluble LAG-3 protein comprises human LAG-3 protein.

9. A combined preparation according to claim 1 , comprising IMP321 and pembrolizumab, or IMP321 and nivolumab.

10. A combined preparation according to claim 1 , wherein the T cells are CD8+ T cells.

11. A pharmaceutical composition comprising:

(a) a soluble LAG-3 protein, or a derivative of LAG-3 protein that is able to bind to MHC class II molecules, wherein the derivative of LAG-3 protein comprises recombinant soluble human LAG-3Ig fusion protein IMP321, wherein the soluble LAG-3 protein or the derivative of LAG-3 protein binds to MHC class II molecules on APCs, thereby activating APCs and further activating T cells;

(b) a programmed cell death protein-1 (PD-1) pathway inhibitor, wherein the PD-1 pathway inhibitor is selected from the group consisting of

pembrolizumab and nivolumab; and

12. The composition of claim 11 , wherein the soluble LAG-3 protein, or the derivative of LAG-3 protein, is present at a unit dosage which is a molar equivalent of 0.25-30 mg of LAG-3Ig fusion protein IMP321.

13. The composition of claim 11 , wherein the PD-1 pathway inhibitor is present at a dose that is up to 50%, 1-50%, 1-25%, or 1-10%, of a typically prescribed dose of the PD-1 pathway inhibitor as a monotherapy, or wherein the PD-1 pathway inhibitor is present at a dose that is 0.1-50%, 0.1-25%, 0.1-20%, 0.1-10%, <20%, <10%, 0.1-<20%, 0.1-<10%, 0.01-<20%, or 0.01-<10% of a typically prescribed dose of the PD-1 pathway inhibitor as a monotherapy.

14. The composition of claim 11 , wherein the soluble LAG-3 protein or the derivative of LAG-3 protein, and the PD-1 pathway inhibitor, are present in any of the combinations of dosage amounts shown in the Table below:

Human dose of LAG-3

protein or the derivative

of LAG-3 protein

Type of

Human dose of

(given as a mg dose of

PD-1 pathway

IMP321, or a molar

inhibitor

inhibitor:

equivalent thereof)

Pembrolizumab

0.07-350 mg

0.25-30 mg

0.07-175 mg

0.25-30 mg

0.07-70 mg

0.25-30 mg

0.07-<70 mg

0.25-30 mg

0.07-35 mg

0.25-30 mg

0.07-7 mg

0.25-30 mg

0.14-350 mg

0.25-30 mg

0.14-175 mg

0.25-30 mg

0.14-70 mg

0.25-30 mg

0.14-<70 mg

0.25-30 mg

0.14-35 mg

0.25-30 mg

0.14-7 mg

0.25-30 mg

Pembrolizumab

0.07-350 mg

1-30 mg

0.07-175 mg

1-30 mg

0.07-70 mg

1-30 mg

0.07-<70 mg

1-30 mg

0.07-35 mg

1-30 mg

0.07-7 mg

1-30 mg

0.14-350 mg

1-30 mg

0.14-175 mg

1-30 mg

0.14-70 mg

1-30 mg

0.14-70 mg

1-30 mg

0.14-<70 mg

1-30 mg

0.14-35 mg

1-30 mg

Pembrolizumab

0.07-350 mg

6-30 mg

0.07-175 mg

6-30 mg

0.07-70 mg

6-30 mg

0.07-<70 mg

6-30 mg

0.07-35 mg

6-30 mg

0.07-7 mg

6-30 mg

0.14-350 mg

6-30 mg

0.14-175 mg

6-30 mg

0.14-70 mg

6-30 mg

0.14-<70 mg

6-30 mg

0.14-35 mg

6-30 mg

0.14-7 mg

6-30 mg

Nivolumab

0.07-350 mg

0.25-30 mg

0.07-175 mg

0.25-30 mg

0.07-70 mg

0.25-30 mg

0.07-<70 mg

0.25-30 mg

0.07-35 mg

0.25-30 mg

0.07-7 mg

0.25-30 mg

0.14-350 mg

0.25-30 mg

0.14-175 mg

0.25-30 mg

0.14-70 mg

0.25-30 mg

0.14-<70 mg

0.25-30 mg

0.14-35 mg

0.25-30 mg

0.14-7 mg

0.25-30 mg

Nivolumab

0.07-350 mg

1-30 mg

0.07-175 mg

1-30 mg

0.07-70 mg

1-30 mg

0.07-<70 mg

1-30 mg

0.07-35 mg

1-30 mg

0.07-7 mg

1-30 mg

0.14-350 mg

1-30 mg

0.14-175 mg

1-30 mg

0.14-70 mg

1-30 mg

0.14-<70 mg

1-30 mg

0.14-35 mg

1-30 mg

0.14-7 mg

1-30 mg

Nivolumab

0.07-350 mg

6-30 mg

0.07-175 mg

6-30 mg

0.07-70 mg

6-30 mg

0.07-<70 mg

6-30 mg

0.07-35 mg

6-30 mg

0.07-7 mg

6-30 mg

0.14-350 mg

6-30 mg

0.14-175 mg

6-30 mg

0.14-70 mg

6-30 mg

0.14-<70 mg

6-30 mg

0.14-35 mg

6-30 mg

0.14-7 mg

6-30 mg.

15. The composition of claim 11 , wherein the soluble LAG-3 protein comprises human LAG-3 protein.

16. A pharmaceutical composition according to claim 11 , comprising IMP321 and pembrolizumab, or IMP321 and nivolumab.

17. A pharmaceutical composition according to claim 11 , wherein the T cells are CD8+ T cells.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 16, 2017

From: TRIEBEL, FREDERIC; BRIGNONE, CHRYSTELLE

To: IMMUTEP S.A.S.

Reel/Frame 043304/0731 →

Priority Claims (1)

GB 1500374.2 · Jan 9, 2015 · national

Continuity (1)

Related Publication 20180271940A1 · Sep 27, 2018

Cited By (2)

US 12,214,012 US 12,673,088