Lipid microparticle growth factor formulations
First Claim
1. An aqueous colloidal lipid microparticle (LMP) pharmaceutical composition comprising water, a therapeutic compound in aqueous media at non-physiological pH, at least one lipid carrier, at least one emulsifying agent, and at least one excipient in an amount to allow titration of the pharmaceutical composition to, and maintain at, physiological pH, wherein the pharmaceutical composition is more soluble and less susceptible to precipitation in aqueous solution at physiological pH than the therapeutic compound, wherein said therapeutic compound comprises at least one hydrophobic GDF-5 related protein which is a naturally occurring or artificially created protein which comprises a cystine-knot-domain with an amino acid identity of at least 70% to the 102 aa cystine-knot-domain of human GDF-5 (amino acids 400-501 of SEQ ID NO:
- 2), wherein the lipid carrier is an oil, and wherein the concentration of the lipid carrier ranges from 5-50 mg/ml.
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Accused Products
Abstract
The present invention is directed to novel formulations and methods for the improved delivery and administration of hydrophobic therapeutic compounds that are substantially insoluble and/or susceptible to precipitation in aqueous solution at physiological pH, including, e.g., growth and differentiation factor-5 and related proteins. Many therapeutic compounds are hydrophobic at physiological pH levels.
5 Citations
66 Claims
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1. An aqueous colloidal lipid microparticle (LMP) pharmaceutical composition comprising water, a therapeutic compound in aqueous media at non-physiological pH, at least one lipid carrier, at least one emulsifying agent, and at least one excipient in an amount to allow titration of the pharmaceutical composition to, and maintain at, physiological pH, wherein the pharmaceutical composition is more soluble and less susceptible to precipitation in aqueous solution at physiological pH than the therapeutic compound, wherein said therapeutic compound comprises at least one hydrophobic GDF-5 related protein which is a naturally occurring or artificially created protein which comprises a cystine-knot-domain with an amino acid identity of at least 70% to the 102 aa cystine-knot-domain of human GDF-5 (amino acids 400-501 of SEQ ID NO:
- 2), wherein the lipid carrier is an oil, and wherein the concentration of the lipid carrier ranges from 5-50 mg/ml.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
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16. An aqueous colloidal lipid microparticle (LMP) pharmaceutical composition comprising a therapeutic compound, a lipid carrier, and an emulsifying agent, wherein said therapeutic compound comprises at least one hydrophobic GDF-5 related protein which is a naturally occurring or artificially created protein which comprises a cystine-knot-domain with an amino acid identity of at least 70% to the 102 aa cystine-knot-domain of human GDF-5 (amino acids 400-501 of SEQ ID NO:
- 2), wherein the lipid carrier is an oil, wherein the concentration of the lipid carrier ranges from 5-50 mg/ml and wherein said pharmaceutical composition comprises lipid microparticles with a size between 0.2 and 100 μ
m. - View Dependent Claims (17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33)
- 2), wherein the lipid carrier is an oil, wherein the concentration of the lipid carrier ranges from 5-50 mg/ml and wherein said pharmaceutical composition comprises lipid microparticles with a size between 0.2 and 100 μ
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34. An aqueous colloidal lipid microparticle (LMP) pharmaceutical composition comprising a therapeutic compound, a lipid carrier, and an emulsifying agent, wherein said therapeutic compound comprises at least one hydrophobic GDF-5 related protein which is a naturally occurring or artificially created protein which comprises a cystine-knot-domain with an amino acid identity of at least 70% to the 102 aa cystine-knot-domain of human GDF-5 (amino acids 400-501 of SEQ ID NO:
- 2), wherein the lipid carrier is an oil, and wherein the concentration of the lipid carrier ranges from 16 to 30 mg/ml.
- View Dependent Claims (35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50)
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51. An aqueous colloidal lipid microparticle (LMP) pharmaceutical composition comprising a therapeutic compound, a lipid carrier, and an emulsifying agent, wherein said therapeutic compound comprises at least one hydrophobic GDF-5 related protein which is a naturally occurring or artificially created protein which comprises a cystine-knot-domain with an amino acid identity of at least 70% to the 102 aa cystine-knot-domain of human GDF-5 (amino acids 400-501 of SEQ ID NO:
- 2), wherein the lipid carrier is an oil, wherein the concentration of the lipid carrier ranges from 5-50 mg/ml and, wherein the concentration of the emulsifying agent ranges from 16 to 30 mg/ml.
- View Dependent Claims (52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66)
Specification