Patent number 8618124 is assigned to
The following quote was obtained by the news editors from the background information supplied by the inventors: "Targeting and drug delivery of therapeutics is becoming increasingly important especially with the use of cytotoxics in the treatment of cancer. A number of methods have been used to selectively target tumors with therapeutic agents to treat cancers in humans and other animals. Targeting moieties such as monoclonal antibodies (mAb) or their fragments have been conjugated to linear polymers via their side chain functional groups. However, this approach usually results in reduced receptor binding affinity either due to changes in the chemical properties of the antibodies or due to folded configuration of polymers that imbed the targeting moiety in the random coiled structure. Ideally, a new conjugate would encompass both a targeting functionality as well as a therapeutic value.
"Recently, heterobifunctional polymeric conjugates having a targeting functional group on one end and a therapeutic moiety (e.g. a chemotherapeutic drug) on the opposite end has been disclosed, see US Patent Application 2002/0197261A1. The polymer conjugates employed have a polymeric spacer bonded to a polymeric carrier containing multiple side-chain functional groups that allow the attachment of multiple drug, molecules (e.g. poly(1-glutamic acid)) on one end, with the other end of the polymeric spacer bonded to a targeting moiety. However, the molecular weight of the polymeric spacer portion is considerably low.
"Methods of preparing higher molecular weight heterobifunctional polymer constructs have been disclosed, see US Patent Application 2002/0072573A1. However, these methods involve the polymerization of monomers which in itself is not ideal due to undesirable polymer dispersity. Other previous methods have involved anionic ethoxylation and difficult purification steps. Attempting to achieve high molecular weight polymer substrates using the techniques above has resulted in poor quality and poor yield of desired product.
"Due to the inadequacies of the present methods there exists a need for improved methods of making high molecular weight heterobifunctional polymer substrates that produce high yield and high purity substrates at the same time retaining low polymer dispersity. It would also be desirable to provide compounds incorporating heterobifunctional polymer substrates as a means of targeting and delivering therapeutically active compounds. The present invention addresses these needs."
In addition to the background information obtained for this patent, NewsRx journalists also obtained the inventors' summary information for this patent: "In one aspect of the invention there are provided compounds of the formula (I):
"X.sub.1-X.sub.6 are independently O, S or NR.sub.1;
"R.sub.44 and R.sub.44' are independently selected polyalkylene oxides;
"R.sub.1 is selected from among hydrogen, C.sub.1-6 alkyls, C.sub.3-12 branched alkyls, C.sub.3-8 cycloalkyls, C.sub.1-6 substituted alkyls, aralkyls, and C.sub.3-8 substituted cycloalkyls;
"R.sub.40-43 are independently selected from among hydrogen, C.sub.1-6 alkyls, C.sub.3-12 branched alkyls, C.sub.3-8 cycloalkyls, C.sub.1-6 substituted alkyls, C.sub.3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C.sub.1-6 heteroalkyls, substituted C.sub.1-6 heteroalkyls, C.sub.1-6 alkoxy, phenoxy and C.sub.1-6 heteroalkoxy;
"y, and y' are independently zero or a positive integer;
"p and p' are independently zero or one;
"n and n' are independently one or a positive integer;
"a and b are independently zero or a positive integer, provided that a+b is greater than or equal to two;
"z is 1 or a positive integer;
"D.sub.1 and D.sub.2 are independently selected from among B, leaving groups, activating groups, OH and terminal groups; and
"B is selected from among biologically active moieties, diagnostic agents and OH.
"In a preferred embodiment, X.sub.1-X.sub.6 are independently Q or NR.sub.1, R.sub.1 is hydrogen, a and b are independently selected integers from 1 to about 20, y and y' are independently 0, 1 or 2, p and p' are each 1, D.sub.1 and D.sub.2 are independently selected from among leaving groups and terminal groups and B, wherein B is a biologically active moiety such as, a drug, an amino or hydroxyl-containing residue, a diagnostic agent such as a dye, chelating agent or isotope labeled compound, a leaving group or activating group.
"For purposes of die present invention, the term 'residue' shall be understood to mean that portion of a biologically active compound which remains after it has undergone a substitution reaction in which the prodrug carrier has been attached.
"For purposes of the present invention, the term 'alkyl' shall be understood to include straight, branched, substituted C.sub.1-12 alkyls, C.sub.3-8 cycloalkyls or substituted cycloalkyls, etc.
"Some of the chief advantages of the present invention include novel high molecular weight heterobifunctional polymeric conjugates capable of enhancing the circulating half-life and solubility of native or unmodified molecules as well as methods of building such conjugates wherein high purity is maintained without needing a chromatography step. Another advantage of the methods of the present invention is the retention of low polymer dispersion with increasing molecular weight of the polymer conjugates. A further advantage of the present invention is that it allows for the artisan to design a drug conjugate that can have the same or different groups on either side of the polymeric portion. This advantage allows the artisan to tailor a compound to contain a delivery or targeting functionality and a therapeutic functionality within the same conjugate depending on a particular need.
"Methods of making and using the compounds and conjugates described herein are also provided."
URL and more information on this patent, see: Greenwald, Richard B.; Zhao,
Keywords for this news article include: Antibodies, Gases, Elements, Hydrogen, Immunology, Therapeutics, Blood Proteins, Immunoglobulins,
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