Lyophilized pharmaceutical compositions for naked DNA gene therapy

A deoxyribonucleic acid, pharmaceutical technology, applied in the field of freeze-dried pharmaceutical compositions for naked deoxyribonucleic acid gene therapy

Active Publication Date: 2020-12-15
HELIXMITH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, even two antisense oligonucleotide drugs for direct injection (nusinersen for intrathecal injection and eteplirsen for intravenous injection) were recently approved , virtually no naked DNA or ribonucleic acid constructs approved for human gene therapy

Method used

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  • Lyophilized pharmaceutical compositions for naked DNA gene therapy
  • Lyophilized pharmaceutical compositions for naked DNA gene therapy
  • Lyophilized pharmaceutical compositions for naked DNA gene therapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0280] Example 1: Lyophilized composition of VM202 (Study 001)

[0281] 1.1 Pharmaceutical composition for trials comprising VM202

[0282] As shown in Table 1 below, various formulations containing VM202 were prepared. The above-mentioned VM202 plasmid as an active ingredient was obtained from frozen stock containing 1.6 mg / mL of VM202 in 0.9% sodium chloride or 1.3 mg / mL of VM202 in 0.9% sodium chloride.

[0283] Table 1

[0284]

[0285] *The control group (control) is the formulation described in US Pat. No. 8,389,492, the entire contents of which are incorporated herein by reference.

[0286] **KP8MS3N and 2MSN are lyophilized dosage forms of the same composition.

[0287] The above-mentioned dosage forms (formulation) are obtained by using materials and devices sold in the market, for example, potassium dihydrogen phosphate (Potassium Phosphate monobasic) (Spectrum, sample number PO200), dipotassium phosphate (PotassiumPhosphate dibasic) (EMD, sample number PX1570-...

Embodiment 2

[0448] Example 2: Lyophilized composition of VM202 (Study 002)

[0449] To test the quality of VM202 in formulations with slight variations in pH and / or concentration of bulking agents and stabilizers, drug product formulations after lyophilization ), various lyophilized formulations containing VM202 were generated and analyzed.

[0450] 2.1 Experimental design

[0451] Material : The active pharmaceutical ingredient (API) examined in this study was VM202. The materials used in this study were structured as follows: The chemicals and materials used to formulate and analyze VM202 are as follows:

[0452] Table 26

[0453]

[0454]

[0455] Formulation parameter : In this study, the following parameters are fixed.

[0456] (1) Fill volume: 5mL

[0457] (2) API concentration: 0.5mg / mL

[0458] (3) Buffer concentration: 10mM potassium phosphate

[0459] (4) Sucrose concentration: 1%

[0460] In the above formulation, the following formulation parameters were exam...

Embodiment 3

[0547] Example 3. Freeze-dried composition of pTx-IGF-1X10

[0548] Among the lyophilized dosage forms, various lyophilized dosage forms containing pTx-IGF-1X10 were generated and analyzed for the quality of pTx-IGF-1X10. Next, the dosage forms listed in Table 37 were prepared for analysis.

[0549] Table 37

[0550] Dosage Form Code buffer pH expansion agent stabilizer PTX-IGF-1X10 concentration F1 10mM potassium phosphate 8 2% Mannitol 1.0% sucrose, 0.45% sodium chloride 0.5mg / ml F2 10mM potassium phosphate 7 2% Mannitol 1.0% sucrose, 0.45% sodium chloride 0.5mg / ml F3 10mM potassium phosphate 9 2% Mannitol 1.0% sucrose, 0.45% sodium chloride 0.5mg / ml F4 10mM potassium phosphate 8 1% Mannitol 1.0% sucrose, 0.45% sodium chloride 0.5mg / ml F5 10mM potassium phosphate 8 2% Mannitol 1.0% sucrose, 0.60% sodium chloride 0.5mg / ml F6 10mM potassium phosphate 8 2% Mannitol 1.0% sucrose, 0.90...

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Abstract

The present invention provides a novel lyophilized pharmaceutical composition that maintains the stability of a DNA plasmid while forming a uniform and elegant cake during lyophilization. The novel lyophilization formulation further allows uniform reconstitution of the DNA plasmid in a pharmaceutically acceptable solution, enabling complete recover of the active ingredients, minimizing partial loss of potency and allowing administration of the active ingredients in an accurate and consistent manner. Additionally provided herein include methods of making the lyophilized pharmaceutical composition and methods of administering the composition for treatment of various diseases.

Description

technical field [0001] The present invention relates to novel lyophilized pharmaceutical compositions which, during lyophilization, form a homogeneous and elegant cake and maintain the stability of deoxyribonucleic acid (DNA) plasmids. [0002] Cross references to related applications [0003] This application claims priority to US Patent Application Serial No. 62 / 700655, filed July 19, 2018, the entire contents of which are incorporated herein by reference. [0004] sequence listing [0005] This application includes the Sequence Listing via EFS-Web, the entire contents of which are hereby incorporated by reference. The name of the ASCII copy made on July 16, 2019 is 40319US_CRF_sequence listing (40319US_CRF_sequencelisting), and the size is 125979 bytes. Background technique [0006] There is actual clinical evidence that concomitant nucleic acid constructs that are not packaged by viruses or virus-like particles (called naked "naked" deoxyribonucleic acid or ribonuclei...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K9/19A61K47/02A61K47/26A61K47/10A61P25/02A61P9/10
CPCA61K9/19A61K47/02A61K31/713A61K38/30A61K38/1833C12N15/85A61K48/0091A61K48/0016A61K2300/00A61K47/26A61K47/10A61P25/02A61P9/10A61K9/0095
Inventor B·S·张
Owner HELIXMITH CO LTD
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