Methods of treating diseases with activated protein c
AssigneeEli Lilly and Company
InventorsAngelina Vucic Ciaccia, Lawrence Mark Gelbert, Brian William Grinnell, Bryan Edward Jones, David Eugene Joyce
Life of this patent
Estimating the term…
Abstract
Method of treating a disease or pathological condition with activated protein C or a compound having activated protein C activity by direct regulation of the expression of specific genes associated with the disease or pathological condition.
Claims18
A method of treating a patient suffering from a disease or pathological condition associated with apoptotic cell death comprising:
- administering a pharmaceutically effective amount of activated protein C or a compound having activated protein C activity.
A method of increasing the activity of Bcl-2 in cells affected by a disease or pathological condition associated with apoptosis which comprises administering a pharmaceutically effective amount of activated protein C or a compound having activated protein C activity.
A method of increasing the activity of human IAP homolog B in cells affected by a disease or pathological condition associated with apoptosis which comprises administering a pharmaceutically effective amount of activated protein C or a compound having activated protein C activity.
Cancelled
A method of increasing angiogenesis in a patient in need of wound healing or tissue repair where PCNA or Gu protein is a regulator of cell growth and survival, comprising:
- administering a pharmaceutically effective amount of activated protein C or a compound having activated protein C activity.
A method of treating a patient suffering from a disease or pathological condition where cell-cell adhesion is a modulator of pathophysiology, comprising:
- administering a pharmaceutically effective amount of activated protein C or a compound having activated protein C activity.
A method of treating a patient suffering from a disease or pathological condition induced by NF-KB which comprises:
- administering a pharmaceutically effective amount of activated protein C or a compound having activated protein C activity.
Use of activated protein C in the manufacture of a medicament for the treatment of a disease or pathological condition associated with apoptotic cell death.
Use of activated protein C in the manufacture of a medicament for the treatment of a disease or pathological condition where:
- PCNA or Gu protein is a regulator of cell growth and survival;
- where cell-cell adhesion is a modulator of pathophysiology;
- or,
- where the disease or pathological condition is induced by NF-kB.
A method of screening to identify test substances which induce or repress expression of genes which are induced or repressed by activated protein C, comprising:
- (i) contacting a cell-with a test substance;
- (ii) monitoring expression of a transcript or its translation product, wherein the transcript specifically hybridizes to one or more genes selected from a first group and a second group, wherein the first group comprises M93718 endothelial ENOS, U29680 Human A1 (bcl-2 homologue), J05614 human proliferating cell nuclear antigen (PCNA) gene, U41387 Human Gu protein mRNA, and U37547 Human IAP homolog B (MHIB) mRNA, complete cds, and the second group comprises Z68228 RDC1, D49824 Human HLA-Bnull allele mRNA, M24736 Human endothelial leukocyte adhesion molecule 1 (ELAM-1), M30257 Human vascular cell adhesion molecule 1 (VCAM-1), X65965 SOD-2 gene for manganese superoxide dimutase, M84739 Human autoantigen calreticulin, M57730 Human B661 mRNA, S76638/U09609 Human nuclear factor kappa-B2 (NF-KB2), X12432 Human major histocompatability complex class 1-type DNA, M59807 Human NK4 mRNA, complete cds, M69043 Homosapiens MAD-3 mRNA encoding IkB-like activity, complete cds, M94880 Human MHU class 1 (HLA-A8001) mRNA, U84487 Human CX3C chemokine precursor, mRNA, alternatively spliced, complete cds, U89922 Human lymphotoxin beta isoform variant, alternatively spliced mRNA, complete cds, wherein a test substance is identified if it increases expression of a transcript which specifically hybridizes to one or more genes in the first group and decreases expression of a transcript which specifically hybridizes to one or more genes in the second group.
A method of screening to identify test substances which modulate the activity of activated protein C on the induction or repression of genes comprising:
- (i) Contacting a cell with a test substance in combination with activated protein C;
- (ii) Monitoring expression of a transcript or its translation product, wherein the transcript specifically hybridizes to one or more genes selected from a first group and a second group, wherein the first group comprises M93718 endothelial ENOS, U29680 Human A1 (bcl-2 homologue), J05614 human proliferating cell nuclear antigen (PCNA) gene, U41387 Human Gu protein mRNA, and U37547 Human IAP homolog B (MHIB) mRNA, complete cds, and the second group comprises Z68228 RDC1, D49824 Human HLA-Bnull allele mRNA, M24736 Human endothelial leukocyte adhesion molecule 1 (ELAM-1), M30257 Human vascular cell adhesion molecule 1 (VCAM-1), X65965 SOD-2 gene for manganese superoxide dimutase, M84739 Human autoantigen calreticulin, M57730 Human B661 mRNA, S76638/U09609 Human nuclear factor kappa-B2 (NF-KB2), X12432 Human major histocompatability complex class 1-type DNA, M59807 Human NK4 mRNA, complete cds, M69043 Homosapiens MAD-3 mRNA encoding IkB-like activity, complete cds, M94880 Human MHU class 1 (HLA-A8001) mRNA, U84487 Human CX3C chemokine precursor, mRNA, alternatively spliced, complete cds, U89922 Human lymphotoxin beta isoform variant, alternatively spliced mRNA, complete cds, wherein a test substance in combination with activated protein C is identified if it increases expression of a transcript which specifically hybridizes to one or more genes in the first group, said increase being greater than with activated protein C alone and decreases expression of a transcript which specifically hybridizes to one or more genes in the second group, said decrease being greater than activated protein C alone.
Dependencies are inferred from the claim text.