Aqueous pharmaceutical composition containing a biologic therapeutic agent and guanidine or a guanidine derivative and an injection including the composition

Patent metadata

Field	Value
Publication number	US-10010513-B2
Application number	US-201313900724-A
Country	US
Kind code	B2
Filing date	May 23, 2013
Priority date	May 25, 2012
Publication date	Jul 3, 2018
Grant date	Jul 3, 2018

Abstract

The present invention is directed to an aqueous pharmaceutical composition, particularly an aqueous ophthalmic composition, suitable as an injection, particularly an intravitreal injection. The composition includes a biologic therapeutic agent (e.g., an isolated monoclonal antibody that specifically binds to a C5 protein) that tends to raise the viscosity of the composition and a guanidine and/or guanidine derivative (e.g., L-arginine) that tends to lower the viscosity of the composition.

First claim

We claim:

1. An aqueous composition suitable for injection, comprising:
at least 50 mg/ml of a biologic therapeutic agent;
guanidine and/or guanidine derivative, wherein the guanidine derivative is arginine; and
wherein the guanidine and/or guanidine derivative is present in the composition at a concentration of at least 25 mM but no greater than 100 mM; and
water;
wherein the composition has a viscosity that is no greater than 10 centipoise, and
wherein the biologic therapeutic agent is an isolated monoclonal antibody that specifically binds to a C5 protein, and
wherein the composition is an aqueous ophthalmic composition suitable for intravitreal injection.

2. A composition as in claim 1 further comprising a stabilizer.

3. A composition as in claim 2 wherein stabilizer is trehalose.

4. A composition as in claim 1 further comprising a surfactant.

5. A composition as in claim 1 wherein the viscosity of the composition is no greater than 7 centipoise.

6. A composition as in claim 1 wherein the guanidine and/or guanidine derivative is L-arginine.

7. A composition as in claim 1 wherein the composition, when containing the biologic therapeutic agent at a concentration of 100 mg/ml, exhibits a viscosity that is at least 3centipoise greater than a viscosity of a substantially identical composition that does not contain the biologic therapeutic agent.

8. A composition as in claim 1 wherein the composition, when containing the guanidine and/or guanidine derivative at a concentration of 50 mM, exhibits a viscosity that is at least 7 cp lower than a viscosity of a substantially identical composition that does not contain the guanidine and/or guanidine derivative.

9. A composition as in claim 1 wherein the biologic therapeutic agent has a molecular weight that is at least 25,000 daltons, but no greater than 500,000.

10. A composition as in claim 1 wherein the biologic therapeutic agent has a molecular weight that is at least 75,000 daltons, but no greater than 125,000.

11. An injection containing an aqueous ophthalmic composition, the injection comprising:
an injection device wherein the injection device includes a chamber defining a containment space and a needle defining a tunnel and wherein the tunnel is in fluid communication with the containment space and wherein the needle has a gauge of at least 25;
an aqueous ophthalmic composition disposed in the containment space of the chamber, the aqueous ophthalmic composition comprising:
i. at least 50 mg/ml of a biologic therapeutic agent, wherein the biologic therapeutic agent is an isolated monoclonal antibody that specifically binds to a C5 protein;
ii. guanidine and/or guanidine derivative, wherein the guanidine derivative is arginine;and
wherein the guanidine and/or guanidine derivative is present in the composition at a concentration of at least 25 mM but no greater than 100 mM; and

iii. water;

wherein the viscosity of the composition is no greater than 7 centipoise and wherein the composition, when containing the biologic therapeutic agent at a concentration of 100 mg/ml, exhibits a viscosity that is at least 7 cp greater than a viscosity of a substantially identical composition that does not contain the biologic therapeutic agent and wherein the composition, when containing the guanidine and/or guanidine derivative at a concentration of 50 mM, exhibits a viscosity that is at least 7 cp lower than a viscosity of a substantially identical composition that does not contain the guanidine and/or guanidine derivative and wherein the biologic therapeutic agent has a molecular weight that is at least 50,000 daltons but no greater than 200,000 daltons and wherein the composition in the containment space has a volume that is at least 16 ml, but no greater than 24 ml.

12. An injection as in claim 11 wherein the biologic therapeutic agent is an IgG1/lambda isotype antibody and the guanidine and/or guanidine derivative is L-arginine.

13. A method of injecting an aqueous pharmaceutical composition, the method comprising:
providing the injection of claim 12 ;
piercing biological tissue of a biologic target with the needle wherein the biologic target is an eye having a vitreous and the biologic tissue is the cornea, the sclera, the conjunctiva or a combination thereof, the biologic target is the eye; and
injecting the composition into the vitreous.

Assignees

• Novartis Ag

Inventors

• Schmitt David
• Wallny Hans-Joachim

Classifications

• A61P27/02

  Ophthalmic agents · CPC title

• A61K9/0048

  Eye, e.g. artificial tears · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K47/20

  containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title