Compositions and Methods for Preventing or Treating Diseases, Conditions, or Processes Characterized by Aberrant Fibroblast Proliferation and Extracellular Matrix Deposition

A composition and characterization technology, which can be applied in drug combinations, urinary system diseases, cardiovascular system diseases, etc., can solve problems such as inability to compensate for MK2 loss, environmental pollution, antitrypsin deficiency, etc.

Inactive Publication Date: 2017-08-29
MOERAE MATRIX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0097] 4. Risk factors
[0098] 4.1. Main risk factors
[0102] 4.1.2. Alpha-1 antitrypsin deficiency
[0105] 4.2.1. Environmental pollution
[0107] 4.2.2. Occupational factors
[0112] 4.3. Other risk factors
[0122] 5.1.1.1 Alcohol consumption
[0158] 6. Renal fibrosis
It is currently unknown whether MK3 plays a similar role, but LPS treatment of MK2-deficient fibroblasts completely abolishes hnRNP AO phosphorylation, suggesting that MK3 is not able to compensate for the loss of MK2

Method used

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  • Compositions and Methods for Preventing or Treating Diseases, Conditions, or Processes Characterized by Aberrant Fibroblast Proliferation and Extracellular Matrix Deposition
  • Compositions and Methods for Preventing or Treating Diseases, Conditions, or Processes Characterized by Aberrant Fibroblast Proliferation and Extracellular Matrix Deposition
  • Compositions and Methods for Preventing or Treating Diseases, Conditions, or Processes Characterized by Aberrant Fibroblast Proliferation and Extracellular Matrix Deposition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0826] Example 1. IC of MMI-0100 (YARAAARQARAKALARQLGVAA; SEQ ID NO: 1) 50 And specificity.

[0827] Use Millipore's IC 50 The Profiler Express service measures the IC of MK2 inhibition (MMI-0100; YARAAARQARAKALARQLGVAA (SEQ ID NO:1)) 50 (Half inhibition concentration) value. This quantitative determination measures how many inhibitors are needed to inhibit 50% of a given biological process or a component of that process (ie, enzymes, cells, or cell receptors) [IC 50 ]. Specifically, in these assays, if the kinase is not inhibited by the inhibitor peptide, the positively charged substrate is phosphorylated by the radiolabeled phosphate group from ATP. The positively charged substrate is then attracted to the negatively charged filter, quantified using a scintillation counter, and compared to a 100% active control.

[0828] Choose an ATP concentration with an apparent Km of ATP within 15 μM, because an ATP concentration close to the Km allows the kinase to have the same relative am...

Embodiment 2

[0842] Example 2. MMI-0100 (YARAAARQARAKALARQLGVAA; SEQ ID NO:

[0843] 1) Preparations and their functional equivalents

[0844] According to some embodiments, MMI-0100 (YARAAARQARAKALARQLGVAA; SEQ ID NO: 1) and its functional equivalent are formulated as a lyophilized powder via spray drying, micronization (eg, jet milling), or as a liquid formulation for spraying.

[0845] Spray drying

[0846] In some embodiments, taking the following factors into consideration, spray drying is used to prepare MMI-0100 (YARAAARQARAKALARQLGVAA; SEQ ID NO: 1) and its functional equivalents:

[0847] (a) Proteins and peptides are prone to denaturation—that is, they break into tertiary structure and sometimes break into secondary structure;

[0848] (b) Denaturation can be reversible or irreversible, and can be caused by various conditions, such as temperature increase, temperature decrease, extreme pH, addition of solvents, pressure, and shear denaturation (this applies to micronization);

[0849] (c) De...

Embodiment 3

[0856] Example 3. Mass production of MMI-0100 (YARAAARQARAKALARQLGVAA; SEQID NO:1) for continuous aerosol performance evaluation

[0857] Perform 2-3 spray drying runs under the defined process parameters described above to generate materials for aerosol performance evaluation.

[0858] The spray-dried powder is well suited for delivery from an inhaler, for example, without limitation, a micro-dose inhaler. For both pure or co-spray dried blends, microdosing utilizes this formulation scheme to routinely achieve high shot doses, as well as both high fine particle fractions and doses. The exemplary aerosol properties of spray dried insulin are shown in figure 1 with 2 in.

[0859] Although dry micronization is the preferred powder production method for small molecules for pulmonary delivery, compared to spray drying, it is a pressure generation method that uses high shear forces. Because the use of high shear forces can lead to the fragmentation of proteins and peptides, dry powderin...

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PUM

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Abstract

The described invention provides compositions and methods for reducing progression of a fibrosis in a tissue of a subject selected from liver, kidney or vascular fibrosis, the progression of the fibrosis being characterized by aberrant fibroblast proliferation and extracellular matrix deposition in the tissue. The method includes administering a therapeutic amount of a pharmaceutical composition containing a polypeptide having the amino acid sequence YARAAARQARAKALARQLGVAA (SEQ ID NO: 1) or functional equivalent thereof, and a pharmaceutically acceptable carrier, wherein the therapeutic amount of the polypeptide is effective to reduce progression of the fibrosis, to treat remodeling of the tissue, or a combination thereof.

Description

[0001] Cross references to related applications [0002] This application requires the United States Provisional Patent Application No. filed on November 17, 2014, entitled "Compositions and methods for preventing or treating diseases, conditions or processes characterized by abnormal fibroblast proliferation and extracellular matrix deposition" 62 / 080,784 and a U.S. utility model patent filed on November 17, 2015 entitled "Composition and method for preventing or treating diseases, conditions or processes characterized by abnormal fibroblast proliferation and extracellular matrix deposition" The priority of application number 14 / 943,752, the content of each of which is incorporated in its entirety by reference. [0003] Statement of government funding [0004] The described invention was completed with government support given to Moerae Matrix, LLC by Small Business Innovation Research (SBIR). The government has certain rights in this invention. Invention field [0005] The present...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61P1/16A61P13/12A61P9/14A61K31/7072
CPCA61K31/7072A61K38/17A61K2300/00A61K31/4025A61K31/427A61K31/506A61K31/513A61P29/00A61P35/00A61K45/06A61K38/16
Inventor C.兰德C.布罗菲
Owner MOERAE MATRIX
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