Injection vehicle for polymer-based formulations

• US 7,651,703 B2
• Filed: 12/21/2006
• Issued: 01/26/2010
• Est. Priority Date: 10/15/1999
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Okumu, Franklin, Lam, Xanthe M., Cleland, Jeffrey L.
• Primary Examiner(s): KAM, CHIH MIN
• Application Number:
  US11/614,462
• Publication Number:
  US 20070098736A1
• Time in Patent Office: 1,132 Days
• Field of Search: 424/488, 424/489, 424/490, 424/497, 514/2, 514/8, 514/12, 514/54, 536/551, 530/324
• US Class Current: 424/489
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61K 38/1866 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0019 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 Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 5/06 of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 2317/55 Fab or Fab'

Abstract

The invention provides injection vehicles suitable for administering particulate suspensions, such as polymer-based formulations, as well as associated pharmaceutical formulations, articles of manufacture, and kits. Other aspects of the invention included methods for producing and administering pharmaceutical formulations. The injection vehicles of the invention are superior to conventional injection vehicles in that they include a pseudoplastic composition that improves injectability, which facilitates delivery of the desired dose. The injection vehicles of the invention also allow the use of smaller-bore needles than are usually necessary to inject polymer-based formulations, reducing the pain associated with injection of such formulations.

Claims

1. A kit comprising:

(a) an injection vehicle comprising hyaluronic acid or sodium hyaluronate dissolved in a physiological buffer at a concentration of about 0.01 to about 3 percent weight per volume; and

(b) particles comprising;

(i) a first component that is a biologically active agent; and

(ii) a second component that is a biocompatible polymeric matrix;

wherein (a) and (b) are dispersed in the same or separate containers adapted for simultaneous administration of (a) and (b) to an animal,

wherein concentration of the particles when combined with the injection vehicle is about 100 to about 500 mg per mL of an injectable formulation formed by combining the injection vehicle and the particles.

2. The kit of claim 1, further comprising a 23 gauge or smaller bore needle.

3. The kit of claim 2, wherein the needle is a 24, 25, 26, 27, 28, or 30 gauge needle.

4. The kit of claim 2, wherein the same or separate containers comprise a sterile access port adapted to receive the needle.

5. The kit of claim 4, wherein the container comprising a sterile access port is a vial or intravenous solution bag.

6. The kit of claim 1, comprising particles at a concentration of 100 to 250 mg per mL of the injectable formulation.

7. The kit of claim 1, wherein the injection vehicle and particles are in different containers.

8. The kit of claim 1, wherein the animal is a mammal.

9. The kit of claim 8, wherein the mammal is a human.

10. The kit of claim 1, further comprising instructions for use.

11. The kit of claim 1, wherein the biologically active agent comprises a polypeptide.

12. The kit of claim 11, wherein the polypeptide is selected from the group consisting of a cytokine;

a cytokine receptor;

a chimeric protein comprising a cytokine or its receptor;

a tumor necrosis factor;

a tumor necrosis factor receptor;

a lipoprotein;

a clotting factor;

an anti-clotting factor;

a serum albumin;

a microbial protein;

a receptor for a hormone;

a receptor for a growth factor;

a rheumatoid factor;

a neurotrophic factor;

a nerve growth factor;

a fibroblast growth factor;

a transforming growth factor (TGF);

a CD protein;

an osteoinductive factor;

an immunotoxin;

a bone morphogenetic protein (BMP);

an interferon;

a colony stimulating factor (CSF);

an interleukin (IL);

a viral antigen;

a transport protein;

a homing receptor;

a regulatory protein;

an antibody;

a chimeric protein;

a plasminogen activator;

a tissue-type plasminogen activator;

a urokinase;

an insulin-like growth factor binding protein;

a T-cell receptor;

a surface membrane protein;

an HIV-1 envelope glycoprotein; and

an immunoadhesin.

13. The kit of claim 11, wherein the polypeptide is pegylated.

14. The kit of claim 11, wherein the polypeptide is selected from the group consisting of tumor necrosis factor-alpha (TNF-alpha);

tumor necrosis factor-beta (TNF-beta);

tumor necrosis factor receptor-1 (TNFR-1);

tumor necrosis factor receptor-2 (TNFR-2);

renin;

human growth hormone;

bovine growth hormone;

growth hormone releasing factor;

parathyroid hormone;

thyroid stimulating hormone;

alpha-1-antitrypsin;

insulin A-chain;

insulin B-chain;

proinsulin;

follicle stimulating hormone;

calcitonin;

luteinizing hormone;

glucagon;

factor VIIIC;

factor IX;

tissue factor;

von Willebrand'"'"'s factor;

Protein C;

atrial natriuretic factor;

lung surfactant;

bombesin;

thrombin;

hemopoietic growth factor;

enkephalinase;

RANTES;

human macrophage inflammatory protein (MIP-1-alpha);

human serum albumin;

mullerian-inhibiting substance;

relaxin A-chain;

relaxin B-chain;

prorelaxin;

mouse gonadotropin-associated peptide;

beta-lactamase;

DNase;

inhibin;

activin;

vascular endothelial growth factor (VEGF);

anti-VEGF Fab;

glucagon-like peptide I (GLP-I);

hepatocyte growth factor (HGF);

integrin;

protein A;

protein D;

bone-derived neurotrophic factor (BDNF);

neurotrophin-3, -4, -5, and -6 (NT-3, NT-4, NT-5, NT-6);

NGF-beta;

platelet-derived growth factor (PDGF);

aFGF;

bFGF;

epidermal growth factor (EGF);

TGF-alpha;

TGF-beta, including TGF-beta1, TGF-beta2, TGF-beta3, TGF-beta4, and TGF-beta5;

insulin-like growth factor-I (IGF-I);

insulin-like growth factor-II (IGF-II);

des (1-3)-IGF-I (brain IGF-I);

CD-3;

CD-4;

CD-8;

CD-19;

erythropoietin;

interferon-alpha;

interferon-beta;

interferon-gamma;

M-CSF;

GM-CSF;

G-CSF;

IL-1;

IL-2;

IL-3;

IL-4;

IL-5;

IL-6;

IL-7;

IL-8;

IL-9;

IL-10;

superoxide dismutase;

decay accelerating factor;

gp120;

gp160; and

addressin.

15. The kit of claim 1, wherein the biologically active agent is an antibody against a tumor-associated antigen.

16. The kit of claim 15, wherein the antibody is an antibody that binds epidermal growth factor receptor (EGFR), ErbB-2 receptor, ErbB-3 receptor, ErbB-4 receptor, or vascular endothelial growth factor (VEGF).

17. The kit of claim 1, wherein the polymeric matrix comprises a biodegradable polymer, a non-biodegradable polymer, a mixture of biodegradable and non-biodegradable polymers, or a copolymer comprising biodegradable and non-biodegradable units.

18. The kit of claim 17, wherein the biodegradable polymer is selected from the group consisting of poly(lactide), poly(glycolide), poly(lactide-co-glycolide), poly(lactic acid), poly(glycolic acid), poly(lactic acid-co-glycolic acid), polyanhydride, polyorthoester, polyetherester, polycaprolactone, polyesteramide, block copolymers of polyethylene glycol and lactide or glycolide, and blends and copolymers thereof.

19. The kit of claim 17, wherein the non-biodegradable polymer is selected from the group consisting of non-biodegradable polyacrylate, polymers of ethylene-vinyl acetate, polymers of acyl-substituted cellulose acetate, non-degradable polyurethane, polystyrene, polyvinyl chloride, polyvinyl fluoride, poly(vinyl imidazole), chlorosulphonate polyolefin, polyethylene oxide, and blends and copolymers thereof.

20. The kit of claim 1, further comprising a second biologically active agent.

21. The kit of claim 1, wherein (b) is lyophilized.

22. The kit of claim 1, wherein the physiological buffer comprises physiological saline.