Abstract

Disclosed herein are linker architectures for conjugates that do not rely on the SAR of the cleavable trigger or the large steric bulk of a closely positioned antibody to alter payload release. These linkers are expected to reduce off-target payload release facilitated by extracellular cathepsins, and may also be applicable to conjugates of antibody fragments that lack the steric protection from a full antibody. In addition, the linkers disclosed herein are expected to provide more selective intracellular payload release. Thus, these linkers can function synergistically with the targeting vector to confer differential payload release rates in vivo that improve the selectivity of intracellular payload release and reduce off target toxicity.

IPC Classes  ?

• A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
• C07D 209/48 - Iso-indolesHydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
• C07C 27/16 - Processes involving the simultaneous production of more than one class of oxygen-containing compounds by oxidation of hydrocarbons with other oxidising agents

Abstract

Disclosed are discrete PEGylated dyes, that is, dyes, generally ones that are fluorescent, but could also include chemi-luminescent or electrochemiluminescent and related dye or dye precursors, that have discrete PEG constructs chemically attached in various configurations on the dye, and in the entire range of constructs, discrete PEG compounds (polyethylene glycol oligomers that are made synthetically according to methods disclosed in U.S. Patent No. 7,888,536 and US Pub. No. 2013/0052130). The dyes are modified in a range of ways to control or optimize the properties of water solubility, non-specific binding (in vitro), biodistribution (in vivo), cell internalization (non-cell or cell based assays in vitro, and in vivo diagnostics and therapy), as well as aggregation.

IPC Classes  ?

• C07C 43/11 - Polyethers containing —O—(C—C—O—)n units with 2 ≤ n ≤ 10
• C09B 23/12 - Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain being branched

Abstract

Disclosed are linear discrete PEG constructs, which can be created and produced in a precise and reproducible way. Key to being able to do these things, where x in the discrete PEGX can vary from about 2 to about 64, is that the processes used to make each linear portion is controlled to give essentially one oligomer/one compound. Having a variable length linear discrete PEG construct that is (a) primarily an linear discrete PEG construct with diagnostic or therapeutic groups attached along a chain of attachment cores, which is attached to a preferential locator; (b) is an m-discrete PEG as the terminal construct on the linear portion, and "hidden"; (c) or linear discrete PEG with a terminus group that can be either negatively or positively charged, or neutral; and any of the discrete PEG portions can be designed to be cleaved after entering the cell.

IPC Classes  ?

• A61K 47/30 - Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
• A61K 51/10 - Antibodies or immunoglobulinsFragments thereof
• A61K 38/00 - Medicinal preparations containing peptides