Compositions and methods for treating bacterial infections with protein-dalbavancin complexes

a technology of dalbavancin and complexes, which is applied in the field of complexes of dalbavancin with endogenous proteins, can solve the problems of limiting the duration of antibacterial activity, and achieve the effect of prolonging the antibacterial

Inactive Publication Date: 2005-01-06
VICURON PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

Still further, the formation of the complex permits systemic tissue distribution of the dalbavancin in a treated patient which is essential to the successful treatment of skin and soft tissue infections.
Without being limited to any theory, it is believed that, in vivo, this c...

Problems solved by technology

Contrarily, many other antibiotic-protein complexes either lose potency upon complex formation and...

Method used

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  • Compositions and methods for treating bacterial infections with protein-dalbavancin complexes
  • Compositions and methods for treating bacterial infections with protein-dalbavancin complexes
  • Compositions and methods for treating bacterial infections with protein-dalbavancin complexes

Examples

Experimental program
Comparison scheme
Effect test

example 1

Efficacy and Safety of Once Weekly Dalbavancin in Deep Skin and Soft Tissue Infections

This randomized, controlled study evaluated the safety and efficacy of two dose regimens of dalbavancin. Adult patients with skin and soft tissue infections (SSTI) involving deep skin structures or requiring surgical intervention were randomized to three groups: Study arm 1 received 1100 mg of dalbavancin via intravenous injection (IV) on day 1; Study arm 2 received 1 g of dalbavancin IV on day 1 and 500 mg of dalbavancin IV on day 8; Study arm 3 received “standard of care.” Clinical and microbiological response and adverse events were assessed.

Populations for Analysis

There were 62 patients randomized into the study; all received at least one dose of study medication. Four study populations were evaluated for safety and efficacy and were defined as follows: The intent-to-treat (ITT) population included all patients who received at least one dose of study drug (all randomized study subjects). ...

example 2

Pharmacokinetics and Renal Excretion of Dalbavancin in Healthy Subjects

The primary objectives of this study were to characterize the pharmacokinetics of dalbavancin and to calculate the extent of renal excretion in healthy subjects receiving a therapeutic dose of the drug. This was an open label, non-comparative, study.

Study Drug Treatment

Healthy male or female subjects between 18 and 65 years of age were administered a single 1000 mg IV dose of dalbavancin infused over 30 minutes.

Six subjects, one female and five male, were enrolled, received study medication, and completed all aspects of the study. Three subjects were Caucasian and three subjects were African-American. Mean age was 29.8 years (range 22 to 63). Mean height was 68.6 inches (range 63 to 75) and mean weight was 179.6 lbs (140 to 244).

Pharmacokinetics

Blood and urine (24-hr collections) were collected on study days 1, 2, 3, 4, 5, 6, 7, 14, 21, 28, and 42. Blood samples were drawn into heparinized tubes and c...

example 3

Protein Binding of Dalbavancin Using Isothermal Titration Microcalorimetry

Binding of dalbavancin to proteins was measured by isothermal titration microcalorimetry (ITC) in 20 mM phosphate, 150 mM NaCl, pH 7.4 at 25 and 37° C. using a Microcal VP-ITC instrument. In a typical experiment, 25×10 μl of protein (˜150 μM) was injected into a calorimeter cell containing dalbavancin solution (˜5 μM). Actual protein and dalbavancin concentrations were determined by measuring absorbence at 280 nm. Control experiments included injections of protein into buffer (in the absence of dalbavancin) to account for the heats of dilution of protein under identical conditions. For comparison, similar experiments with some necessary modifications were performed using teicoplanin.

Experiments with dalbavancin were conducted with each of the following proteins: human albumin; dog albumin; rat albumin; bovine albumin; and human α-glycoprotein. Teicoplanin was studied with human albumin and α-glycoprotein. ...

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Abstract

The invention provides methods and compositions for treatment of bacterial infections. Methods of the invention include administration of dalbavancin for treatment of a bacterial infection, in particular a Gram-positive bacterial infection of skin and soft tissue, under conditions where a protein-dalbavancin complex forms, or administering a protein-dalbavancin complex. Dosing regimes include once weekly administration of dalbavancin, which often remains at therapeutic levels in the bloodstream for at least one week, providing prolonged therapeutic action against a bacterial infection.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention This invention is directed to complexes of dalbavancin with endogenous proteins. These complexes can be formed in vivo, in vitro, or ex vivo and provide for an antimicrobial effect in a treated patient. 2. State of the Art According to the U.S. Center for Disease Control and Prevention, nosocomial bloodstream infections are a leading cause of death in the United States. Approximately five percent of the seven million central venous catheters (CVCs) inserted annually in the United States are associated with at least one episode of bloodstream infection (approximately 350,000 a year). Catheter-related bloodstream infections occur when bacteria enter the bloodstream through an intravenous catheter and can be life threatening. Skin and soft tissue infections (SSTIs) are a common medical condition and often the consequence of trauma or surgical procedures. Staphylococcus aureus and Streptococcus pyogenes are the pathogens most fr...

Claims

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Application Information

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IPC IPC(8): A61K31/70A61K31/704A61K38/12A61K38/14A61P31/04
CPCA61K31/70A61K31/704A61K38/00A61K38/14A61K2300/00A61P31/00A61P31/04
Inventor CAVALERI, MARCOCOLOMBO, LUIGIHENKEL, TIMOTHYJABES, DANIELAMALABARBA, ADRIANOMOSCONI, GIORGIOSTOGNIEW, MARTINWHITE, RICHARD J.
Owner VICURON PHARM INC
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