Exogenously triggered controlled release materials and uses thereof

• US 8,846,103 B2
• Filed: 01/27/2010
• Issued: 09/30/2014
• Est. Priority Date: 01/28/2009
• Status: Active Grant

• Current Assignee: SmartCells, Inc. (Merck & Co., Inc.)
• Original Assignee: SmartCells, Inc. (Merck & Co., Inc.)
• Inventors: Zion, Todd C., Lancaster, Thomas M.
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): SAMALA, JAGADISHWAR RAO
• Application Number:
  US13/145,530
• Publication Number:
  US 20120046223A1
• Time in Patent Office: 1,707 Days
• Field of Search: 514/3, 514/19, 514/23, 514 53- 54, 435/6, 435/7.1, 435/196, 424/488, 424/486, 424/489, 424/490, 424/493
• US Class Current: 424/493
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

The disclosure provides cross-linked materials that include multivalent cross-linking agents that bind an exogenous target molecule; and conjugates that include two or more separate affinity ligands bound to a conjugate framework, wherein the two or more affinity ligands compete with the exogenous target molecule for binding with the cross-linking agents and wherein conjugates are cross-linked within the material as a result of non-covalent interactions between cross-linking agents and affinity ligands on different conjugates. The conjugates also include a drug.

Claims

1. A cross-linked material comprising:

multivalent cross-linking agents that are capable of binding an exogenous target molecule that includes a saccharide; and

conjugates that include a drug and two or more separate affinity ligands bound to a polymeric conjugate framework, wherein

(i) the two or more affinity ligands are capable of competing with the exogenous target molecule for binding with the cross-linking agents;

(ii) the conjugates are cross-linked within the material as a result of non-covalent interactions between the cross-linking agents and the affinity ligands on different conjugates;

(iii) wherein each affinity ligand includes a saccharide; and

(iv) the conjugate is of the general formula;

2. The material of claim 1, wherein the affinity ligands of the conjugates include a saccharide selected from glucose, mannose, glucosamine, mannosamine, methylglucose, methylmannose, ethylglucose, and ethylmannose.

3. The material of claim 1, wherein the affinity ligands of the conjugates include a bimmanose or branched trimannose.

4. The material of claim 1, wherein the affinity ligands of the conjugates include aminoethylglucose (AEG), aminoethylmannose (AEM), aminoethylfucose (AEF), aminoethylbimannose (AEBM), or aminoethyltrimannose (AETM).

5. The material of claim 1, wherein the multivalent cross-linking agents include a lectin.

6. The material of claim 5, wherein the lectins are covalently bonded to a recognition element, wherein the recognition element competes with the exogenous target molecule and affinity ligands of the conjugate for binding to the lectin, and the lectin has a higher affinity for the affinity ligands of the conjugate than for the recognition element.

7. The material of claim 6, wherein the exogenous target molecule is a saccharide and both the affinity ligands of the conjugate and the recognition element include a saccharide.

8. The material of claim 1, wherein the multivalent cross-linking agents include a peptide aptamer.

9. The material of claim 1, wherein the multivalent cross-linking agents include a polynucleotide aptamer.

10. The material of claim 1, wherein the drug is an insulin molecule.

11. A method comprising administering a material of claim 1 to a patient and subsequently administering a triggering amount of the exogenous target molecule to the patient.