Therapeutic uses of protein-polymer conjugates

A technology of conjugates and uses, applied in the direction of peptide/protein components, animal/human proteins, active ingredients of heterocyclic compounds, etc.

Active Publication Date: 2014-10-15
PHARMAESSENTIA CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Other disadvantages include low water solubility and induction of neutralizing antibodies

Method used

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  • Therapeutic uses of protein-polymer conjugates
  • Therapeutic uses of protein-polymer conjugates
  • Therapeutic uses of protein-polymer conjugates

Examples

Experimental program
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specific Embodiment approach

[0062] Preparation of di-PEG aldehyde

[0063]

[0064] 20kD PEGO(C=O)OSu was prepared from 20kD mPEGOH purchased from (SunBio Inc., CA, USA) according to the method described in Bioconjugate Chem. 1993, 4, 568-569.

[0065] A solution of 6-(1,3-dioxolan-2-yl)hexane-1,5-diamine in dichloromethane (11.97 g solution containing 9.03 mg diamine, 47.8 μmol) was added to a solution containing 20 kD PEGO (C=O)OSu (1.72 g, 86.0 μmol) in a flask. After complete dissolution of PEGO(C=O)OSu, N,N-diisopropylethylamine (79 μL, 478 μmol) was added. The reaction mixture was stirred at room temperature for 24 hours, then methyl tert-butyl ether (200 mL) was added dropwise with stirring. The resulting precipitate was collected and dried under vacuum to yield the bis-PEG acetal (1.69 g, 98%) as a white solid.

[0066] 1 H NMR (400MHz, d 6 -DMSO) δ7.16(t, J=5.2Hz, 1H), 7.06(d, J=8.8Hz, 1H), 4.76(t, J=4.8Hz, 1H), 4.10-3.95(m, 4H), 1.80-1.65 (m, 1H), 1.65-1.50 (m, 1H), 1.48-1.10 (m, 6H)....

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Abstract

The present invention relates to the use of the protein-polymer conjugate described in the specification to treat various diseases, including primary myelofibrosis, polycythemia vera and essential thrombocythemia.

Description

[0001] Cross References to Relevant Application Paragraphs [0002] This application claims priority to US Provisional Application No. 61 / 285,411, filed December 10, 2009, the contents of which are hereby incorporated by reference in their entirety. Background technique [0003] Advances in cell biology and recombinant protein technology have led to the development of protein therapeutics. [0004] However, major obstacles remain. Most proteins are prone to proteolytic degradation and therefore have a short half-life in the circulation. Other disadvantages include low water solubility and induction of neutralizing antibodies. [0005] Attaching polymers such as polyethylene glycol (PEG) to proteins prevents proteolytic enzymes from accessing the protein backbone, resulting in increased protein stability. In addition, it also improves water solubility and minimizes immunogenicity. Efficient methods of linking polymers to proteins are therefore needed. Brief description of...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/40A61K38/21A61P35/00A61P31/12A61P31/00
CPCA61K38/212A61K47/48215C07K14/56A61K31/40A61K47/60A61P25/00A61P31/00A61P31/12A61P31/14A61P31/20A61P35/00A61P43/00A61P7/00
Inventor K-C·林R·威德曼
Owner PHARMAESSENTIA CORP
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