Multifunctional zwitterionic polymer conjugates

Abstract

The present invention provides random copolymers containing zwitterions and one or more functional agents, and methods of preparing such random copolymers.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application No. 61 / 288,127, filed Dec. 18, 2009.BACKGROUND OF THE INVENTION[0002]An arms race of sorts is happening right now amongst the pharmaceutical companies who are all trying to deliver ‘medically differentiated products’. Current drug formats are inflexible, in that they generally allow for a single activity. For example, a recombinant monoclonal antibody generally is designed and optimized to bind and inhibit a single target protein. For example, a small molecule drug is generally designed and optimized to bind and activate (or inhibit) a single target. In some cases, the drug is not selective and there are multiple activities (for example, a small molecule kinase inhibitor that is designed to bind the ATP binding site of a single kinase but which shows a level of affinity and bioactivity against adjacent kinase family members). But generally drug developers optimize using tod...

AI Technical Summary

Benefits of technology

The present invention provides random copolymers with specific monomers that can form new topologies through non-covalent binding, such as chelation or pH sensitivity. The copolymers can also have different reactivity ratios for the monomers, allowing for the formation of alternating, periodic, gradient, block, or statistical copolymers. Additionally, the copolymers can have a tunable linking group that allows for the release of functional agents in response to predefined triggers such as aqueous or low pH environments. The random copolymers can be used in various applications such as drug delivery, sensors, and biomimetic materials.

Problems solved by technology

Current drug formats are inflexible, in that they generally allow for a single activity.

In addition, the technology should allow for certain of the bioactive moieties to be unstably attached such that they can be released under the desired conditions (time, aqueous pH environment, other).

However, even where direct administration, such as by injection, of biologically active agents is possible, formulations may be unsatisfactory for a variety of reasons including the generation of an immune response to the administered agent and responses to any excipients including burning and stinging.

Even if the active agent is not immunogenic and satisfactory excipients can be employed, biologically active agents can have a limited solubility and short biological half-life that can require repeated administration or continuous infusion, which can be painful and / or inconvenient.

Less frequent dosing reduces the overall number of injections, which can be painful and which require inconvenient visits to healthcare professionals.

Although some success has been achieved with PEG conjugation, “PEGylation” of biologically active agents remains a challenge.

As drug developers progress beyond very potent agonistic proteins such as erythropoietin and the various interferons, the benefits of the PEG hydrophilic polymer are insufficient to drive the increases in solubility, stability and the decreases in viscosity and immunogenicity that are necessary for a commercially successful product that is subcutaneously administered.

PEG conjugation may also result in the loss of biological activity.

While branched polymers may overcome some of the problems associated with conjugates formed with long linear PEG polymers, neither branched nor linear PEG polymer conjugates completely resolve the issues associated with the use of conjugated functional agents.

Both linear and branched PEG conjugates can, for example, suffer from rates of degradation that are either too long or too short.

A rapid rate of degradation can result in a conjugate having too short of an in vivo half-life, whereas, too slow of a rate of degradation can result in an unacceptably long conjugate half-life in vivo.

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