摘要:
The present invention provides fusion polypeptides comprising polypeptide ligands that are modified by circular permutation and fused to at least one polypeptide fusion partner wherein such fusion polypeptides have new, improved or enhanced biological functions or activities. Such improvements include, but are not limited to, increased binding affinity, increased activity, increased agonist activity (super agonist), antagonist activity, increased accessibility, increased flexibility of the active site, increased stability, broader and/or changed substrate specificity, and combinations thereof.
摘要:
The present disclosure relates to an exendin-4 analogue PEGylated with polyethylene glycol or a derivative thereof, a preparation method, and a pharmaceutical composition for prevention or treatment of diabetes containing the same as an active ingredient. According to the present invention, the yield of an exendin-4 analogue can be increased via the selective PEGylation by using exendin-4 in which a cysteine is introduced into #40 site of the C-terminal, and treatment effect of medications can be increased, so that the exendin-4 analogue can be usefully applied as a composition for prevention or treatment of diseases caused by insulin hypersecretion.
摘要:
The present invention provides stably cross-linked insulionotropic polypeptides having superior and unexpected benefits in the treatment of conditions involving abnormal glucose homeostasis, e.g., type 2 diabetes and conditions relating to type 2 diabetes. Such benefits include, but are not limited to, extended polypeptide half-life, enhanced alpha-helicity, improved thermal stability and protease resistance, increased functional activity and pharmacologic properties, improved bioavailability when administered by any route, and improved bioavailability and gastrointestinal absorption when delivered orally, as compared to the corresponding unmodified polypeptides. The invention also provides compositions for administering the polypeptides of the invention, as well as methods for preparing and evaluating the polypeptides of the invention.
摘要:
The present invention provides fusion polypeptides comprising polypeptide ligands that are modified by circular permutation and fused to at least one polypeptide fusion partner wherein such fusion polypeptides have new, improved or enhanced biological functions or activities. Such improvements include, but are not limited to, increased binding affinity, increased activity, increased agonist activity (super agonist), antagonist activity, increased accessibility, increased flexibility of the active site, increased stability, broader and/or changed substrate specificity, and combinations thereof.
摘要:
A method of generating conditionally active biologic antibodies from parent antibodies, in particular therapeutic antibodies, which are more active at an aberrant physiological condition than at a normal physiological condition and which may reversibly or irreversibly inactivated at the wild type normal physiological condition. For example, evolved antibodies are may be less active or inactive at normal body temperature or pH, than at other aberrant body temperatures or at an aberrant pH.
摘要:
The invention relates to a gene transfer-based method to protect a subject from diabetes or obesity. The method comprises administering to a salivary gland of the subject an AAV virion comprising an AAV vector that encodes an exendin-4 protein. Also provided are exendin-4 proteins and nucleic acid molecules that encode such exendin-4 proteins. Also provided are AAV vectors and AAV virions that encode an exendin-4 protein. One embodiment is an exendin-4 protein that is a fusion protein comprising an NGF secretory segment joined to the amino terminus of an exendin-4 protein domain.
摘要:
Peptide-grafted antibodies having agonist activity against a Class B GPCR and their uses, and methods for identifying same. Mammalian cell lines for high-throughput screening for agonists of a Class B GPCR are also provided that comprise a stably integrated recombinant nucleic acid construct comprising a reporter gene under control of a cAMP responsive promoter, the reporter gene encoding a cell surface expressed protein, and a stably integrated recombinant nucleic acid construct comprising a sequence encoding a Class B GPCR under control of a constitutive promoter.
摘要:
Disclosed herein are immunoglobulin fusion proteins that have a first antibody region attached to an extender fusion region. The extender fusion region contains a therapeutic agent and a beta strand secondary structure. The extender fusion region may contain 7 or fewer consecutive amino acids based on or derived from an ultralong CDR3. Alternatively, the extender fusion region contains a rigid stalk protein structure, but does not contain an amino acid sequence based on or derived from an ultralong CDR3. The extender fusion region may also have one or more linkers or proteolytic cleavage sites. The immunoglobulin fusion proteins may have additional therapeutic agents and extender fusion regions. Also disclosed herein are pharmaceutical compositions of immunoglobulin fusion proteins and methods for using the immunoglobulin fusion proteins for the treatment or prevention of a disease or condition in a subject.
摘要:
Methods of generating fusion protein variants are provided that comprise introducing sequence diversity at the junction region or regions in the fusion and allows for the generation of variants having a desired activity. Examples include immunoglobulins comprising a domain or polypeptide inserted into, or replacing, a CDR. Also provided are polynucleotides encoding a fusion protein and comprising two or more RSSs, and compositions and host cells comprising same, as well as fusion proteins variants produced by the described methods.