Multi-layered injectable self-assembling peptide scaffold hydrogels for long-term sustained release of human antibodies
First Claim
1. A sustained release formulation comprising;
- (i) a gel core comprising a self-assembling first peptide and a therapeutic antibody, wherein the self-assembling first peptide has an amino acid sequence selected from the group consisting of Ac-(RADA)2-CONH2 (SEQ ID NO;
1), Ac-(RADA)3-CONH2 (SEQ ID NO;
2), Ac-(RADA)4-CONH2 (SEQ ID NO;
3), and Ac-(RADA)5-CONH2 (SEQ ID NO;
4); and
,(ii) a first layer encapsulating said gel core, wherein said first layer comprises a self-assembling second peptide, wherein the self-assembling second peptide has an amino acid sequence selected from the group consisting of Ac-(KLDL)3-CONH2 (SEQ ID NO;
7), Ac-(KLDL)4-CONH2 (SEQ ID NO;
8) and Ac-(KLDL)5-CONH2 (SEQ ID NO;
9).
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Abstract
The invention relates to a pharmaceutical formulation for sustained delivery of a therapeutic agent, preferably a protein, polypeptide, an antibody or an antibody fragment, comprising one or more gel forming peptides wherein the formulation exhibits sustained delivery for at least two weeks, three weeks, four weeks, five weeks, six weeks, seven weeks, eight weeks, nine weeks, ten weeks, eleven weeks, twelve weeks or more. In one embodiment, the invention relates to a formulation comprising self-assembling peptides that undergo sol-gel transition in the presence of an electrolyte solution such as biological fluids and salts. The formulation can provide sustained release of antibody and antibody fragments, in particular, IgG. Antibody diffusivities can be decreased with increasing hydrogel nanofiber density, providing a means to control the release kinetics.
34 Citations
28 Claims
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1. A sustained release formulation comprising;
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(i) a gel core comprising a self-assembling first peptide and a therapeutic antibody, wherein the self-assembling first peptide has an amino acid sequence selected from the group consisting of Ac-(RADA)2-CONH2 (SEQ ID NO;
1), Ac-(RADA)3-CONH2 (SEQ ID NO;
2), Ac-(RADA)4-CONH2 (SEQ ID NO;
3), and Ac-(RADA)5-CONH2 (SEQ ID NO;
4); and
,(ii) a first layer encapsulating said gel core, wherein said first layer comprises a self-assembling second peptide, wherein the self-assembling second peptide has an amino acid sequence selected from the group consisting of Ac-(KLDL)3-CONH2 (SEQ ID NO;
7), Ac-(KLDL)4-CONH2 (SEQ ID NO;
8) and Ac-(KLDL)5-CONH2 (SEQ ID NO;
9). - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 28)
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15. A process for preparing a controlled release formulation comprising the steps of;
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a. preparing a first solution comprising a self-assembling first peptide, and an antibody or antibody fragment, wherein the self-assembling first peptide has an amino acid sequence selected from the group consisting of Ac-(RADA)2-CONH2 (SEQ ID NO;
1), Ac-(RADA)3-CONH2 (SEQ ID NO;
2), Ac-(RADA)4-CONH2 (SEQ ID NO;
3), and Ac-(RADA)5-CONH2 (SEQ ID NO;
4);b. forming a gel core; c. coating said gel core with a self-assembling second peptide solution, wherein the self-assembling second peptide has an amino acid sequence selected from the group consisting of Ac-(KLDL)3-CONH2 (SEQ ID NO;
7), Ac-(KLDL)4-CONH2 (SEQ ID NO;
8) and Ac-(KLDL)5-CONH2 (SEQ ID NO;
9); and
,d. forming a layer encapsulating said first self-assembled gel core. - View Dependent Claims (16, 17, 18, 19, 20, 21)
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22. A process for preparing a controlled release formulation comprising the steps of:
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a. preparing a first solution comprising a self-assembling first peptide, and a therapeutic agent, wherein the self-assembling first peptide has an amino acid sequence selected from the group consisting of Ac-(RADA)2-CONH2 (SEQ ID NO;
1), Ac-(RADA)3-CONH2 (SEQ ID NO;
2), Ac-(RADA)4-CONH2 (SEQ ID NO;
3), and Ac-(RADA)5-CONH2 (SEQ ID NO;
4);b. forming a self-assembled gel core; c. coating said gel core with a self-assembling second peptide, wherein the second peptide has an amino acid sequence selected from the group consisting of Ac-(KLDL)3-CONH2 (SEQ ID NO;
7), Ac-(KLDL)4-CONH2 (SEQ ID NO;
8) and Ac-(KLDL)5-CONH2 (SEQ ID NO;
9); and
,d. forming a layer encapsulating said gel core. - View Dependent Claims (23, 24, 25, 26, 27)
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Specification