Abstract: The disclosure provides improved ADAMTS13 variants with amino acid substitutions in the linker 3 region. The disclosure also provides methods for producing and using the variants.

Abstract: Inhibitor compounds are disclosed. The compounds are effective in the treatment of diseases or conditions in which interleukin 1 ? activity is implicated. Methods of synthesis of the compounds, as well as pharmaceutical compositions comprising the compounds are also disclosed.

Abstract: A method for delivering permeant substances transdermally into a membrane of an animal includes forming at least one delivery opening in the skin tissue, with the at least one delivery opening having a mean opening depth of between about 40 and about 90 microns.

Abstract: Inhibitor compounds are disclosed. The compounds are effective in the treatment of diseases or conditions in which interleukin 1 ? activity is implicated. Methods of synthesis of the compounds, as well as pharmaceutical compositions comprising the compounds are also disclosed.

Abstract: A transdermal permeant delivery of at least one permeant composition into a tissue membrane of a subject including a disposable substrate having at least a portion of a bottom surface of a first release liner connected to an upper surface of the substrate and a patch having a backing layer and a reservoir that is selectively removable from the top surface of the first release liner. In a connected position, a first portion of the backing layer of the patch is releaseably mounted to a top surface of the first release liner in spaced registration with a poration area of the substrate.

Abstract: Providing a method for monitoring an analyte extracted from a patient and delivering a permeant composition to the patient. The method includes the steps of a) contacting a poration device to a tissue membrane of the patient, the poration device including at least one porator array; b) actuating poration of the tissue membrane using the at least one porator array in the poration device; c) extracting the analyte from the porated tissue membrane by way of the at least one porator array; d) analyzing the analyte to determine a concentration of the analyte within the tissue membrane; and e) delivering a permeant composition to the tissue membrane by way of the at least one porator array.

Abstract: A method for delivering permeant substances transdermally into a membrane of an animal includes forming at least one delivery opening in the skin tissue, with the at least one delivery opening having a mean opening depth of between about 40 and about 90 microns.

Abstract: A transdermal permeant delivery of at least one permeant composition into a tissue membrane of a subject including a disposable substate having at least a portion of a bottom surface of a first release liner connected to an upper surface of the substrate and a patch having a backing layer and a reservoir that is selectively removable from the top surface of the first release liner. In a connected position, a first portion of the backing layer of the patch is releaseably mounted to a top surface of the first release liner in spaced registration with a poration area of the substate.

Abstract: A method for delivering permeant substances transdermally into a membrane of an animal includes forming at least one delivery opening in the skin tissue, with the at least one delivery opening having a mean opening depth of between about 40 and about 90 microns.

Abstract: Providing a method for monitoring an analyte extracted from a patient and delivering a permeant composition to the patient. The method includes the steps of a) contacting a poration device to a tissue membrane of the patient, the poration device including at least one porator array; b) actuating poration of the tissue membrane using the at least one porator array in the poration device; c) extracting the analyte from the porated tissue membrane by way of the at least one porator array; d) analyzing the analyte to determine a concentration of the analyte within the tissue membrane; and e) delivering a permeant composition to the tissue membrane by way of the at least one porator array.

Abstract: The invention provides for a device for delivering a drug comprising: a. forming one or more micropores in a tissue membrane; and b. applying a patch containing a drug to the one or more micropores formed in the tissue membrane The invention also provides for methods of making and methods of using the same.

Abstract: A transdermal permeant delivery system for delivery of at least one permeant composition into a tissue membrane of a subject including a disposable substrate having at least a portion of a bottom surface of a first release liner connected to an upper surface of the substrate and a patch having a backing layer and a reservoir that is selectively removable from the top surface of the first release liner. In a connected position, a first portion of the backing layer of the patch is releaseably mounted to a top surface of the first release liner in spaced registration with a poration area of the substrate.

Abstract: The invention provides for an integrated device for forming a cavity in a surface of a tissue of an animal comprising: a) a controller board connected to an energy source for actuating at least one porator; b) a fluid reservoir in fluid communication with the tissue; and c) a tissue interface layer, the tissue interface layer containing the at least one porator, the porator in contact with the tissue for forming the cavity. The invention also provides for methods of making and methods of using the same.

Abstract: A method for delivering permeant substances transdermally into a membrane of an animal includes forming at least one delivery opening in the skin tissue, with the at least one delivery opening having a mean opening depth of between about 40 and about 90 microns.

Abstract: A transdermal permeant delivery system for delivery of at least one permeant composition into a tissue membrane of a subject including a disposable substrate having at least a portion of a bottom surface of a first release liner connected to an upper surface of the substrate and a patch having a backing layer and a reservoir that is selectively removable from the top surface of the first release liner. In a connected position, a first portion of the backing layer of the patch is releaseably mounted to a top surface of the first release liner in spaced registration with a poration area of the substrate.

Abstract: A transdermal permeant delivery system for delivery of at least one permeant composition into a tissue membrane of a subject including a disposable substrate having at least a portion of a bottom surface of a first release liner connected to an upper surface of the substrate and a patch having a backing layer and a reservoir that is selectively removable from the top surface of the first release liner. In a connected position, a first portion of the backing layer of the patch is releaseably mounted to a top surface of the first release liner in spaced registration with a poration area of the substrate.

Abstract: The invention provides for an integrated device for forming a cavity in a surface of a tissue of an animal comprising: a) a controller board connected to an energy source for actuating at least one porator; b) a fluid reservoir in fluid communication with the tissue; and c) a tissue interface layer, the tissue interface layer containing the at least one porator, the porator in contact with the tissue for forming the cavity. The invention also provides for methods of making and methods of using the same.

Abstract: A method for delivering permeant substances transdermally into a membrane of an animal includes forming at least one delivery opening in the skin tissue, with the at least one delivery opening having a mean opening depth of between about 40 and about 90 microns.

Abstract: The invention provides for an integrated device for forming a cavity in a surface of a tissue of an animal comprising: a) a controller board connected to an energy source for actuating at least one porator; b) a fluid reservoir in fluid communication with the tissue; and c) a tissue interface layer, the tissue interface layer containing the at least one porator, the porator in contact with the tissue for forming the cavity. The invention also provides for methods of making and methods of using the same.

Abstract: A transdermal permeant delivery system for delivery of at least one permeant composition into a tissue membrane of a subject including a disposable substrate having at least a portion of a bottom surface of a first release liner connected to an upper surface of the substrate and a patch having a backing layer and a reservoir that is selectively removable from the top surface of the first release liner. In a connected position, a first portion of the backing layer of the patch is releaseably mounted to a top surface of the first release liner in spaced registration with a poration area of the substrate.