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Compositions and methods for preventing or treating chronic lung allograft dysfunction and idiopathic pulmonary fibrosis

An allogeneic, dysfunctional technology, applied in chemical instruments and methods, drug combinations, antibodies, etc., to solve problems such as environmental pollution, incomplete understanding of specificity, and antitrypsin deficiency

Inactive Publication Date: 2017-02-22
MOERAE MATRIX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0098] 4. Risk factors
[0099] 4.1. Main risk factors
[0103] 4.1.2. Alpha-1 antitrypsin deficiency
[0105] 4.2. Related risk factors
[0106] 4.2.1. Environmental pollution
[0108] 4.2.2. Occupational factors
[0113] 4.3. Other risk factors
The reasons for the specificity exhibited by CIP are not fully understood

Method used

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  • Compositions and methods for preventing or treating chronic lung allograft dysfunction and idiopathic pulmonary fibrosis
  • Compositions and methods for preventing or treating chronic lung allograft dysfunction and idiopathic pulmonary fibrosis
  • Compositions and methods for preventing or treating chronic lung allograft dysfunction and idiopathic pulmonary fibrosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0678] Example 1. IC of MMI-0100 (YARAAARQARAKALARQLGVAA; SEQ ID NO: 1) 50 and specificity.

[0679] ICs using Millipore 50 Profiler Express Service Determination of IC for MK2 Inhibition (MMI-0100; YARAAARQARAKALARQLGVAA (SEQ ID NO: 1)) 50(half inhibitory concentration) value. This quantitative assay measures how much inhibitor is required to inhibit a given biological process or a component of that process (i.e., enzyme, cell, or cell receptor) by 50% [IC 50 ]. Specifically, in these assays, if the kinase is not inhibited by an inhibitory peptide, the positively charged substrate is phosphorylated by a radiolabeled phosphate group from ATP. Positively charged substrates are then attracted to negatively charged filters, quantified using a scintillation counter, and compared to 100% active controls.

[0680] An ATP concentration within 15 μΜ of ATP's apparent Km was chosen because ATP concentrations close to this Km would allow the kinase to have the same relative amount ...

Embodiment 2

[0695] Example 2. MMI-0100 (YARAAARQARAKALARQLGVAA; SEQ ID NO:

[0696] 1) and preparations of functional equivalents thereof

[0697] According to some embodiments, MMI-0100 (YARAAARQARAKALARQLGVAA; SEQ ID NO: 1 ) and functional equivalents thereof are formulated as a lyophilized powder via spray drying, micronization (eg, jet milling), or as a liquid formulation for spraying.

[0698] spray drying

[0699] In some embodiments, spray drying is used to prepare MMI-0100 (YARAAARQARAKALARQLGVAA; SEQ ID NO: 1 ) and functional equivalents thereof, taking into account the following factors:

[0700] (a) proteins and peptides are prone to denaturation, i.e., fragmentation into tertiary structure and sometimes into secondary structure;

[0701] (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 micronizatio...

Embodiment 3

[0709] Example 3. Mass production of MMI-0100 (YARAAARQARAKALARQLGVAA; SEQID NO: 1) for continuous aerosol performance evaluation

[0710] 2-3 spray drying runs were performed under the defined process parameters described above to generate material for aerosol performance evaluation.

[0711] Spray-dried powders are well suited for delivery from an inhaler, such as, without limitation, a microdose inhaler. Microdosing utilizes this formulation scheme to routinely achieve high shot doses, and both high fine particle fractions and doses, for both neat or co-spray-dried blends. Exemplary aerosol properties of spray-dried insulin are shown in figure 1 with 2 middle.

[0712] While dry micronization is the preferred method of powder production for small molecules for pulmonary delivery, it is a pressure-generating method that uses high shear compared to spray drying. Dry powdering is generally not used for large molecules because the use of high shear forces can lead to fragme...

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Abstract

The described invention provides compositions and methods for reducing lung allograft dysfunction after lung transplant and for treating a severe pulmonary fibrosis characterized by aberrant fibroblast proliferation and extracellular matrix deposition in a tissue of a subject. The methods comprise administering to a subject in need thereof a composition comprising an antibody component comprising a therapeutic amount of an anti-CD44 antibody; and an MK2 inhibitor component comprising a therapeutic amount of an MK2 inhibitor (MK2i) polypeptide of amino acid sequence YARAAARQARAKALARQLGVAA (SEQ ID NO: 1) or at least one peptide functionally equivalent to the therapeutic domain thereof selected from a polypeptide of amino acid sequence KALARQLAVA (SEQ ID NO: 8), a polypeptide of amino acid sequence KALARQLGVA (SEQ ID NO: 9) and a polypeptide of aminoacid sequence KALARQLGVAA (SEQ ID NO: 1), or a functional equivalent thereof, and a pharmaceutically acceptable carrier.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of priority of US Provisional Application 61 / 953,438 (filed March 14, 2014), the contents of which are incorporated by reference in their entirety. [0003] Statement of Government Funding [0004] The invention was made with government support from Small Business Innovation Research (SBIR) awarded to Moerae Matrix, LLC and from NHLBI PO1 awarded to Dr. Noble. The Government has certain rights in this invention. [0005] field of invention [0006] The present invention is in the fields of cellular and molecular biology, polypeptides, and methods of therapeutic use. Background technique [0007] 1. Mechanisms of wound healing and fibrosis [0008] The term "wound healing" refers to the process by which the body repairs any trauma to its tissues, especially those caused by physical means and with a break in continuity. [0009] The wound healing response is often described as havin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K38/17A61K38/08
CPCA61K38/005A61K39/39541C07K16/2884C07K2317/76A61K38/08A61K9/0075A61K9/0078A61K2039/505A61P11/00A61P29/00A61P37/06A61P43/00A61K2300/00
Inventor C.布罗菲C.兰德P.W.诺布尔
Owner MOERAE MATRIX