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Amphoteric liposomesRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Preparations Characterized By Special Physical Form, LiposomesAmphoteric liposomes description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070104775, Amphoteric liposomes. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority from U.S. Provisional Application Ser. No. 60/717,199, filed on Sep. 15, 2005; European Application No. 05020218.3, filed on Sep. 15, 2005; European Application No. 05020217.5, filed on Sep. 15, 2005; PCT Application No. PCT/EP2005/011905, filed on Nov. 4, 2005; PCT Application No. PCT/EP2005/011908, filed on Nov. 4, 2005; U.S. application Ser. No. 11/266,999, filed on Nov. 4, 2005; U.S. application Ser. No. 11/267,423, filed on Nov. 4, 2005; European Application No. 06113784.0, filed on May 10, 2006; and European Application No. 05090322.8, filed on Nov. 21, 2005. [0002] Each of the applications and patents cited in this text, as well as each document or reference cited in each of the applications and patents (including during the prosecution of each issued patent; "application cited documents"), and each of the U.S. and foreign applications or patents corresponding to and/or claiming priority from any of these applications and patents, and each of the documents cited or referenced in each of the application cited documents, are hereby expressly incorporated herein by reference. More generally, documents or references are cited in this text, either in a Reference List before the claims, or in the text itself; and, each of these documents or references ("herein-cited references"), as well as each document or reference cited in each of the herein-cited references (including any manufacturer's specifications, instructions, etc.), is hereby expressly incorporated herein by reference. Documents incorporated by reference into this text may be employed in the practice of the invention. FIELD OF THE INVENTION [0003] The present invention relates to amphoteric liposomes and has particular reference to such liposomes having improved stability in human or animal serum. The present invention also comprehends mixtures of lipids capable of encapsulating active agents or ingredients such, for example, as drugs to form liposomes and pharmaceutical compositions comprising such liposomes. BACKGROUND OF THE INVENTION [0004] Oligonucleotides represent a novel class of drugs that can very specifically down-regulate or interfere with protein expression. Such oligonucleotides include antisense, locked nucleic acids (LNA), peptide nucleic acids (PNA), morpholino nucleic acids (Morpholinos), small interfering RNAs (siRNA) and transcription factors decoys of various chemistries. A detailed description of the different mechanisms of action of such oligonucleotide therapeutics can be found in the literature (e.g., Crooke in BBA (1999), 1489(1), 3144; Tijsterman, et al. in Cell (2004), 117(1), 1-3; and Mann, et al. in J Clin Invest, (2000), 106(9), 1071-5). [0005] The use of oligonucleotides for gene repair applications (see, e.g., Richardson, et al. in Stem Cells (2002), 20, 105-118) and micro RNAs are other examples from this rapidly growing field. [0006] It is known in the art that nucleic acid therapeutics, irrespective of their actual chemical origin, may lack therapeutic efficacy owing to their instability in body fluids or because of inefficient uptake into cells, or both. Chemical modifications of such oligonucleotide, including the above-mentioned variants, as well as the formation of conjugates with ligands or polymers, represent one strategy to overcome such practical limitations. [0007] A second set of strategies involves the use of carrier systems, in particular liposomes, for protecting, targeting and affording enhanced uptake into cells. Liposomes are artificial single, oligo or multilamellar vesicles having an aqueous core and being formed from amphiphilic molecules having both hydrophobic and hydrophilic components (amphiphiles). The cargo may be trapped in the core of the liposome, disposed in the membrane layer or at the membrane surface. Such carrier systems should meet an optimum score of the following criteria: high encapsulation efficiency and economical manufacture, colloidal stability, enhanced uptake into cells and of course low toxicity and immunogenicity. [0008] Anionic or neutral liposomes are often excellent in terms of colloidal stability, as no aggregation occurs between the carrier and the environment. Consequently their biodistribution is excellent and the potential for irritation and cytotoxicity is low. However, such carriers lack encapsulation efficiency and do not provide an endosomolytic signal that facilitates further uptake into cells (Journal of Pharmacology and experimental Therapeutics (2000), 292, 480-488 by Klimuk, et al.). [0009] A great many of publications deal with cationic liposomal systems; see, e.g., Molecular Membrane Biology (1999), 16, 129-140 by Maurer, et al.; BBA (2000) 1464, 251-261 by Meidan, et al.; Reviews in Biology and Biotechnology (2001), 1(2), 27-33 by Fiset & Gounni. Although cationic systems provide high loading efficiencies, they lack colloidal stability, in particular after contact with body fluids. Ionic interactions with proteins and/or other biopolymers lead to in situ aggregate formation with the extracellular matrix or with cell surfaces. Cationic lipids have often been found to be toxic as shown by Filion, et al. in BBA (1997), 1329(2), 345-356; Dass in J. Pharm. Pharmacol. (2002), 54(5), 593-601; Hirko, et al. in Curr. Med. Chem., 10(14), 1185-1193. [0010] These limitations were overcome by the addition of components that provide a steric stabilisation to the carriers. Polyethylenglycols of various chain length, for example, are known to eliminate aggregation problems associated with the use of cationic components in body fluids, and PEGylated cationic liposomes show enhanced circulation times in vivo (BBA (2001) 1510, 152-166 by Semple, et al.). However, the use of PEG does not solve the intrinsic toxicity problems associated with cationic lipids. It is also known that PEG substantially inhibits the productive entry of such liposomes into the cells or their intracellular delivery (Song, et al. in BBA (2002), 1558(1), 1-13). Quite recently, Morrissey, et al. (Nature Biotechnology (2005), 23 (8), 1002-1007) described a diffusible PEG-lipid for a cationic vector that is able to transfer siRNA into liver cells in vivo. However, the huge demand for such solutions and the given attrition rate of clinical development more than motivates the development of conceptually independent solutions. [0011] Amphoteric liposomes represent a recently described class of liposomes having an anionic or neutral charge at pH 7.5 and a cationic charge at pH 4. WO 02/066490, WO 02/066012 and WO 03/070735, all to Panzner, et al. and incorporated herein by reference, give a detailed description of amphoteric liposomes and suitable lipids therefor. Further disclosures are made in WO 03/070220 and WO 03/070735, also to Panzner, et al. and incorporated herein by reference, which describe further pH sensitive lipids for the manufacture of such amphoteric liposomes. [0012] Amphoteric liposomes have an excellent biodistribution and are very well tolerated in animals. They can encapsulate nucleic acid molecules with high efficiency. [0013] The use of amphoteric liposomes as carriers for drugs for the prevention or treatment of different conditions or diseases in mammals requires stability of the liposomes after their injection into the bloodstream. For systemic applications especially, the drug must be stably encapsulated in the liposomes until eventual uptake in the target tissue or cells. The FDA's guidelines prescribe specific preclinical tests for drugs comprising liposomal formulations (http://www.fda.gov/cder/guidance/2191dft.pdf). For example, the ratio of encapsulated drug to free drug must be determined during the circulation time in the bloodstream. [0014] After the injection of liposomes into the bloodstream, serum components interact with the liposomes and may lead to permeabilisation of the liposomal membrane. However, the release of a drug that is encapsulated by the liposome also depends upon the molecular dimensions of the drug. This means that a plasmid drug with a size of thousands of base pairs, for example, may be released much more slowly than smaller oligonucleotides or other small molecules. For liposomal delivery of drugs it is essential that the release of the drug during the circulation of the liposomes is as low as possible. OBJECTS OF THE INVENTION [0015] An object of the present invention therefore is to provide liposomes and mixtures of lipids capable of forming such liposomes having improved stability upon contact with human or animal serum. [0016] In particular, an object of the present invention is to provide amphoteric liposomes having such improved serum stability. [0017] Another object of the invention is to provide pharmaceutical compositions comprising such liposomes as a carrier for the targeted delivery of active agents or ingredients, including drugs such as nucleic acid drugs, e.g., oligonucleotides and plasmids. [0018] A particular object of the present invention is to provide such a pharmaceutical composition for the treatment or prophylaxis of inflammatory, immune or autoimmune disorders of humans or non-human animals. [0019] Yet another object of the present invention is provide methods for the treatment of human or non-human animals in which a pharmaceutical composition comprising an active agent is targeted to a specific organ or organs, tumours or sites of infection or inflammation. SUMMARY OF THE INVENTION Continue reading about Amphoteric liposomes... Full patent description for Amphoteric liposomes Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Amphoteric liposomes patent application. ###
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