Novel cellular factor-containing solution compositions

a technology of cellular factor and solution composition, which is applied in the direction of drug composition, antibacterial agent, peptide/protein ingredient, etc., can solve the problems of cytokines and growth factors and other protein-based therapeutics being more difficult to administer to patients than other pharmaceuticals, and affecting the safety of patients, so as to reduce variability, increase production yield, and reduce the effect of variability

Inactive Publication Date: 2009-02-26
STEMNION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0012]The pooled cell-derived compositions possess several important properties and characteristics including decreased variability in the levels of physiologically relevant cellular factors necessary for therapeutic effect as compared to non-pooled compositions. The cellular factors are present in levels comparable to physiological levels found in the body and are thus optimal for use in therapeutic applications which require intervention to support, initiate, replace, accelerate or otherwise influence biochemical and biological processes involved in the treatment and / or healing of disease and / or injury. The novel methods described herein of pooling cell-derived compositions to decrease variability has the effect of optimizing levels of the secreted factors such that their full therapeutic potential can be achieved in every pool. In addition to the therapeutic value of such pooled compositions, the method of pooling samples to decrease non-pooled composition-to-composition variability has the significant commercial advantages of increasing production yields by minimizing non-pooled composition rejection for failure to meet product specifications and, consequently, decreasing production costs and increasing revenues.

Problems solved by technology

Unfortunately, the results have been only partially encouraging.
Failures include BDNF, CNTF and IGF-1 which have all been evaluated in clinical trials designed to test their efficacy in treating ALS, each with disappointing results; TGFβ2 was unsuccessful in a phase 2 study for venous ulcers; and IGF-1 and PDGF combination therapy was unsuccessful in diabetic foot ulcers.
Also, because of the complex interaction between cytokines and growth factors in a given physiological niche, the application of just one factor, especially one at abnormally high levels, cannot recreate the physiological niche and may, in fact, grossly disturb its delicate balance.
Compounding their limited success in the clinic, cytokines and growth factors and other protein-based therapeutics are typically more difficult to administer to patients than other pharmaceuticals.
Unfortunately, drawbacks to using organic solvents are their tendency to cause protein denaturation.
To date, no protein-based therapeutic agent (i.e. cytokines and growth factors) is available that effectively recreates or mimics the complex combination and physiologic levels of physiologically relevant cytokines and growth factors found naturally in the body in healthy and disease or injury states.
In addition, no one has yet been able to administer these physiologically relevant cytokines and growth factors at physiological levels.
Further, no one has yet been able to administer these physiologically relevant cytokines and growth factors at physiological levels in a sustained-release formulation.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Preparation of AMP Cell Compositions

[0119]Recovery of AMP cells—AMP cells were dissociated from starting amniotic membrane using the dissociation agents PXXIII, and trypsin. The average weight range of an amnion was 18-27 g. The number of cells recovered per g of amnion was about 10-15×106 for dissociation with PXXIII and 5-8×106 for dissociation with trypsin.

[0120]Method of obtaining selected AMP cells: Cells were plated immediately upon isolation from the amnion. After ˜2 days in culture non-adherent cells were removed and the adherent cells were kept. This attachment to a plastic tissue culture vessel is the selection method used to obtain the desired population of AMP cells. Adherent and non-adherent AMP cells appear to have a similar cell surface marker expression profile but the adherent cells have greater viability and are the desired population of cells. Adherent AMP cells were cultured until they reached ˜120,000-150,000 cells / cm2. At this point, the cultures were confluent...

example 2

Generation of ACCS

[0121]The AMP cells of the invention can be used to generate ACCS, including pooled ACCS. The AMP cells were isolated as described above and ˜1×106 cells / mL were seeded into T75 flasks containing ˜10 mL culture medium. The cells were cultured until confluent, the medium was changed and ACCS was collected 3 days post-confluence. Skilled artisans will recognize that other embodiments for collecting ACCS from confluent cultures, such as using other tissue culture vessels, including but not limited to cell factories, flasks, hollow fibers, or suspension culture apparatus, etc. are also contemplated by the methods of the invention (see Detailed Description above). It is also contemplated by the instant invention that the ACCS be cryopreserved, lyophilized or formulated for sustained-release following collection. It is also contemplated that ACCS be collected at different time point (see Detailed Description for details).

example 3

Generation of Pooled ACCS

[0122]ACCS was obtained essentially as described above. In certain embodiments, ACCS was collected multiple times from an AMP cell culture derived from one placenta and these multiple ACCS collections were pooled together. Such pools are referred to as “SP pools” (more than one ACCS collection / one placenta). In another embodiment, AMP cell cultures were derived from several placentas, i.e. from 5 or 10 placentas. The AMP cells from each placenta were cultured and one ACCS collection from each culture was collected and then they were all pooled. These pools are termed “MPI pools” (one ACCS collection / placenta, multiple placentas). In yet another embodiment, AMP cell cultures were derived from several placentas, i.e. from 5 or 10 placentas. The AMP cells from each placenta were cultured and more than one ACCS collection was performed from each AMP cell culture and then pooled. These pools are termed “MP2 pools” (more than one ACCS collection / placenta, multiple...

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Abstract

The invention is directed to novel cellular factor-containing solution compositions (referred to herein as “CFS” compositions), including novel sustained-release cellular factor-containing solution compositions (referred to herein as “SR-CFS” compositions), methods of making such novel compositions and uses thereof.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001]This application claims priority under 35 USC §119(e) of U.S. Provisional Application Nos. 60 / 965,707, filed Aug. 22, 2007, and 61 / 125,960, filed Apr. 30, 2008, the entireties of which are incorporated herein by reference.FIELD OF THE INVENTION [0002]The field of the invention is directed to novel cellular factor-containing solution compositions (referred to herein as “CFS” compositions), including novel sustained-release cellular factor-containing solution compositions (referred to herein as “SR-CFS” compositions), methods of making such novel compositions and uses thereof.BACKGROUND OF THE INVENTION [0003]Many individual cytokines and growth factors have been evaluated for their therapeutic utility in the treatment of many varied diseases, disorders and injuries. Unfortunately, the results have been only partially encouraging. For example, PDGF-BB has proven to be useful in the treatment of diabetic foot ulcers; GM-CSF is marketed in E...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/18A61P43/00
CPCA61K38/1841A61K38/1858A61K38/1866A61K38/1891A61K38/57A61K2300/00A61P17/02A61P43/00
Inventor MARSHALL, VIVIENNE S.SMITH, CHARLOTTE A.TRUMPOWER, CATHERINE J.SING, GEORGE L.PALLADINO, LINDA O.
Owner STEMNION
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