Characterizing a glatiramer acetate related drug product

A method of identifying suboptimal activity of a glatiramer acetate related drug substance or drug product comprising the steps of:

• a) administering a glatiramer acetate related drug substance or drug product to a rodent;
• b) determining the level of biological activity of the rodent selected from the group consisting of, immune response to antigen presenting cells, differentiation of effector lymphocytes, suppression of T lymphocytes, activation of Foxp3 positive regulatory T cells, expansion of mononuclear leukocytes, proliferation of T lymphocytes, expansion of lymphocytes, differentiation of naïve lymphocytes, inflammatory response, adhesion of immune cells, cell movement, migration of cells, chemotaxis of cells, cell movement of phagocytes, chemotaxis of monocytes, cell movement of monocytes and fever,
• or determining the level of expression in the rodent of one or more genes selected from the group consisting of Ecm1, Pres1, Pdlim4, Gpr83, Ifng, Il24, LOC100046608, Gm590, Gpr114, Tmie, Rasgrp1, Myo6, Pfkp, Usp18, Arl4c, Als2cl, 2810410P22Rik, Arl5a, Gbp2, Rasgrp1, Ankrd37, Tpil, 4930583H14Rik, Ifit3, LOC667370, Klhdc1, Cd247, Igfbp4, Oas2, Bcl11b, Fscn1, Ctsg, Mpo, Prtn3, Lyzs, Emr1, Chi3l1, Anxa3, Hp, Lyz2, Lyz, Fer1l3, Sirpa, Cd63, Clec4n, Clec4d, EG433016, Stfa1, Chi3l3 Ngp, S100a8, S100a9, Clecsf9, Saa3, 5033414K04Rik, Slc7a11, Slpi, Cd14, Fpr2, Fcgr3, F10, Gpnmb, Tgfbi, Mmp14, Slcllal, C3, Gpr84, Acta2, Lcn2, Hmox1, Tsab1, Ccl14, Il2, Inhba, Cxcl1, Serpinb2, Upp1, Gpr109a, Gp38, Il1b, Cxcl2, Il1a, Ccl3, 6720418B01Rik, 5830496L11Rik, Cd8b1, Fcgrt, LOC385615 and Scml4;
• determining the level of expression of one or more genes selected from the group consisting of the genes presented in Table 8;
• determining the level of expression of one or more genes selected from the group consisting of the genes presented in Table 10;
• determining the level of expression of one or more genes selected from the group consisting of FoxP3, GPR83, CD14, TLR2, IFNG, CD40 and IL1B;
• determining the level of expression of one or more genes selected from the group consisting of the genes presented in Table 12;
• or determining gene set enrichment analysis for genes associated with at least one cell type selected from the group consisting of FoxP3+ CD4+ T cells, CD4+ T cells CD8+ T cells, gamma delta T cells, natural killer T cells, CD4+ CD8+ T cells, macrophage cells, monocyte cells stromal cells, multi-lineage progenitor cells, dendritic cells, fibroblastic reticular cells, fibroblasts and granulocytes;
• and
• c) identifying the glatiramer acetate related drug substance or drug product as causing a suboptimal activity if the level of biological activity selected from the group consisting of immune response to antigen presenting cells, differentiation of effector lymphocytes, suppression of T lymphocytes and activation of Foxp3 positive regulatory T cells is decreased relative to a reference standard or if the level of biological activity selected from the group consisting of expansion of mononuclear leukocytes, proliferation of T lymphocytes, expansion of lymphocytes, differentiation of naïve lymphocytes, inflammatory response, adhesion of immune cells, cell movement, migration of cells, chemotaxis of cells, cell movement of phagocytes, chemotaxis of monocytes, cell movement of monocytes and fever is increased relative to a reference standard,
• or identifying the glatiramer acetate related drug substance or drug product as causing a suboptimal activity if the level of expression of a gene selected from the group consisting of Ecm1, Pres1, Pdlim4, Gpr83, Ifng, Il24, LOC100046608, Gm590, Gpr114, Tmie, Rasgrp1, Myo6, Pfkp, Usp18, Arl4c, Als2cl, 2810410P22Rik, Arl5a, Gbp2, Rasgrp1, Ankrd37, Tpi1, 4930583H14Rik, Ifit3, LOC667370, Klhdc1, Cd247, Igfbp4, Oas2 Bcl11b, 6720418B01Rik, 5830496L11Rik, Cd8b1, Fcgrt, LOC385615 and Scml4 is decreased relative to a reference standard or if the level of expression of a gene selected from the group consisting of Fscn1, Ctsg, Mpo, Prtn3, Lyzs, Emr1, Chi3l1, Anxa3, Hp, Lyz2, Lyz, Fer1l3, Sirpa, Cd63, Clec4n, Clec4d, EG433016, Stfa1, Chi3l3 Ngp, S100a8, S100a9, Clecsf9, Saa3, 5033414K04Rik, Slc7a11, Slpi, Cd14, Fpr2, Fcgr3, F10, Gpnmb, Tgfbi, Mmp14, Slc11a1, C3, Gpr84, Acta2, Lcn2, Hmox1, Tsab1, Ccl4, Il2, Inhba, Cxcl1, Serpinb2, Upp1, Gpr109a, Gp38, Il1b, Cxcl2, Il1a, and Ccl3, is increased relative to a reference standard;
• identifying the glatiramer acetate related drug substance or drug product as causing a suboptimal activity if the level of expression of a gene selected from the group consisting of the genes presented in Table 8 is not substantially identical to the level of expression of a reference standard;
• identifying the glatiramer acetate related drug substance or drug product as causing a suboptimal activity if the level of expression of a gene selected from the group consisting of the genes presented in Table 10 is not substantially identical to the level of expression of a reference standard;
• identifying the glatiramer acetate related drug substance or drug product as causing a suboptimal activity if the level of expression of a gene selected from the group consisting of GPR83, IFNG and Foxp3 is decreased or if the level of expression of a gene selected from the group consisting of CD14, CD40, TLR2 and IL1B is increased;
• identifying the glatiramer acetate related drug substance or drug product as causing a suboptimal activity if the level of expression of a gene selected from the group consisting of the genes identified in Table 12 as FoxP3+ T cell genes is decreased or if the level of expression of a gene selected from the group consisting of the genes identified in Table 12 as macrophage genes and the genes identified in Table 12 as monocyte genes is increased;
• or identifying the glatiramer acetate related drug substance or drug product as causing a suboptimal activity if gene set enrichment analysis indicates downregulation or a lack of upregulation for genes associated with at least one cell type selected from the group consisting of FoxP3+ CD4+ T cells, CD4+ T cells CD8+ T cells, gamma delta T cells, natural killer T cells and CD4+ CD8+ T cells or if gene set enrichment analysis indicates upregulation or a lack of downregulation for genes associated with at least one cell type selected from the group consisting of macrophage cells, monocyte cells stromal cells, multi-lineage progenitor cells, dendritic cells, fibroblastic reticular cells, fibroblasts and granulocytes
• thereby identifying suboptimal activity of a glatiramer acetate related drug substance or drug product.