ADP-ribosyl transferase fusion proteins, pharmaceutical compositions, and methods of use
AssigneeBioaxone Therapeutique Inc.
InventorLisa McKerracher
Life of this patent
Estimating the term…
Abstract
The Rho family GTPases regulates axon growth and regeneration. Inactivation of Rho with C3, a toxin from Clostridium botulinum, can stimulate regeneration and sprouting of injured axons. The present invention provides novel chimeric C3-like Rho antagonists. These new antagonists are a significant improvement over C3 compounds because they are 3-4 orders of magnitude more potent to stimulate axon growth on inhibitory substrates than recombinant C3. The invention further provides evidence that these compounds promote repair when applied to the injured mammalian central nervous system.
Claims25
A pharmaceutical composition comprising;
- a) a polypeptide consisting of SEQ ID NO:
- 43 and;
- b) a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising;
- a) a polypeptide comprising an amino acid sequence of a transport agent covalently linked to an amino acid sequence of an active agent, said amino acid sequence of said active agent consisting of ADP-ribosyl transferase C3 or a fragment thereof retaining ADP-ribosyl transferase activity, said amino acid sequence of said transport agent facilitating uptake of the active agent by a receptor-independent mechanism and being selected from the group consisting of a subdomain of HIV Tat protein, a homeodomain of antennapedia, and a Histidine tag, and
- b) a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising;
- a) a polypeptide comprising an amino acid sequcncc of a transport agent covalently linked to an amino acid sequence of an active agent, said amino acid sequence of said active agent consisting of ADP-ribosyl transferase C3 or a fragment thereof retaining ADP-ribosyl transferase activity, said amino acid sequence of said transport agent facilitating uptake of the active agent by a receptor-independent mechanism and being selected from the group consisting of SEQ IDNO:21, SEQ ID NQ:26, SEQ IDNO:31, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, ftnd SEQ ID NO:
- 47, and SEQ ID NO:
- 48 and
- b) a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising;
- a) a polypeptide comprising an amino acid sequence of a transport agent covalently linked to an amino acid sequence of an active agent, said amino acid sequcncc of said active agent consisting of ADP-ribosyl transferase C3 or an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO:
- 43 and retaining ADP-ribosyl transferase activity, said amino acid sequence of said transport agent facilitating uptake of the active agent by a receptor-independent mechanism and being selected from the group consisting of a subdomain of HIV Tat protein, a homeodomain of antennapedia, and a Histidine tag, and
- b) a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising;
- a) a polypeptide comprising an amino acid sequence of a transport agent covalently linked to an amino acid sequence of an active agent, said amino acid sequence of said active agent consisting of ADP-ribosyl transferase C3 or an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEO ID NO:
- 43 and rctaining ADP-ribosyl transferase activity, said amino acid sequence of said transport agent facilitating uptake of the active agent by a receptor-independent mechanism and being selected from the group consisting of SEQ ID NO:21, SEQ ID NO:26, SEQ ID NO:31, SEQ ID NO:44, SEQ ID NO:45, SEQ IDNO:46, SEQ ID NO:
- 47, and SEQ ID NO:
- 48, and
- b) a pharmaceutically acceptable carrier.
A substantially purified polypeptide comprising an amino acid sequence of a transport agent covalently linked to an amino acid sequence of an active agent, said amino acid sequence of said active agent consisting of ADP-ribosyl transferase C3 or a fragment thereof retaining ADP-ribosyl transferase activity, said amino acid sequence of said transport agent facilitating uptake of the active agent by a receptor-independent mechanism and being selected from the group consisting of a subdomain of HIV Tat protein, a homeodomain of antennapedia, and a Histidine tag, said polypeptide having ADP-ribosyl transferase activity.
A substantially purified polypeptide comprising an amino acid sequence of a transport agent covalently linked to an amino acid sequence of an active agent, said amino acid sequence of said active agent consisting of ADP-ribosyl transferase C3 or a fragment thereof retaining ADP-ribosyl transferase activity, said amino acid sequence of said transport agent facilitating uptake of the active agent by a receptor-independent mechanism and being selected from the group consisting of SEQ ID NO:21, SEQ ID NO:26, SEQ ID NO:31, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:
- 47, and SEQ ID NO:
- 48, said polypeptide having ADP-ribosyl transferase activity.
A substantially purified polypeptide comprising an amino acid sequence of a transport agent covalently linked to an amino acid sequence of an active agent, said amino acid sequence of said active agent consisting of ADP-ribosyl transferase C3 or an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO:
- 43 and retaining ADP-ribosyl transferase activity, said amino acid sequence of said transport agcnt facilitating uptake of the activc agent by a receptor-independent mechanism and being selected from the group consisting of a subdomain of HIV Tat protein, a homeodomain of antennapedia, and a Histidine tag, said polypeptide having ADP-ribosyl transferase activity.
A substantially purified polypeptide comprising an amino acid sequence of a transport agent covalently linked to an amino acid sequence of an active agent, said amino acid sequence of said active agent consisting of ADP-ribosyl transferase C3 or an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO:
- 43 and retaining ADP-ribosyl transferase activity, said amino acid sequence of said transport agent facilitating uptake of the active agent by a receptor-independent mechanism and being selected from the group consisting of SEQ ID NO:21, SEQ ID NO:26, SEQ ID NO:31, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:
- 47, and SEQ ID NO:
- 48, said polypeptide having ADP-ribosyl transferase activity.
Dependencies are inferred from the claim text.