The present application relates to optimized IgG immunoglobulin variants, engineering methods for their generation, and their application, particularly for therapeutic purposes.

FC variants with altered binding to FCRN

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

Modulators of atp-binding cassette transporters

Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

Heterocyclic compounds and uses thereof

The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetases that can incorporate unnatural amino acids into proteins in mammalian host cells, for example, primate host cells and rodent host cells. The invention provides, for example but not limited to, translation systems that include host cells (e.g., primate or rodent cells), orthogonal aminoacyl-tRNA synthetases derived from eubacterial synthetases, orthogonal tRNAs, and the unnatural amino acid. The invention also relates to methods for producing proteins of interest comprising at least one unnatural amino acid in mammalian host cell systems.

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Genetic incorporation of unnatural amino acids into proteins in mammalian cells

The present invention is directed to diabody molecules and uses thereof in the treatment of a variety of diseases and disorders, including immunological disorders, infectious disease, intoxication and cancers. The diabody molecules of the invention comprise two polypeptide chains that associate to form at least two epitope binding sites, which may recognize the same or different epitopes on the same or differing antigens. Additionally, the antigens may be from the same or different molecules. The individual polypeptide chains of the diabody molecule may be covalently bound through non-peptide bond covalent bonds, such as, but not limited to, disulfide bonding of cysteine residues located within each polypeptide chain. In particular embodiments, the diabody molecules of the present invention further comprise an Fc region, which allows antibody-like functionality to engineered into the molecule.

Covalent Diabodies and Uses Thereof

Modified interferon polypeptides with at least one non-naturally-encoded amino acid and uses thereof are provided.

Modified Human Interferon Polypeptides and Their Uses

Modified biosynthetic polypeptide molecules, methods for manufacturing, and uses thereof are provided.

Biosynthetic polypeptides utilizing non-naturally encoded amino acids

The present invention provides chemical entities or compounds and pharmaceutical compositions thereof that are capable of modulating certain protein kinases such as mTor, tyrosine kinases, and/or lipid kinases such as PI3 kinase. Also provided in the present invention are methods of using these compositions to modulate activities of one or more of these kinases, especially for therapeutic applications.

Kinase inhibitors and methods of use

The present invention provides modified human growth hormone polypeptides of which amino acid sequence is SEQ ID NO: 2, comprising hGH polypeptides of one non-naturally encoded amino acids. The non-naturally encoded amino acids are substituted at a residue position of 35 of the SEQ ID NO: 2, the human growth hormone polypeptides are in covalent linkage with a 30kDa straight chain polyethylene glycol molecule through an oxime bond, wherein the oxime bond is formed between the non-naturally encoded amino acids and the polyethylene glycol molecule, the non-naturally encoded amino acids are p-acetyl-phenylalanine.

Modified Human Growth Hormone Polypeptides and Their Uses

Provided is a method of producing a functional four helical bundle (4HB) polypeptide comprising at least one non-naturally encoded amino acid by (i) providing at least one orthogonal tRNA and an mRNA encoding a 4HB polypeptide, said mRNA comprising at least one selector codon at one or more selected positions in said mRNA, wherein at least one selector codon is recognizable by at least one orthogonal tRNA; and (ii) aminoacylating the at least one orthogonal tRNA with at least one orthogonal tRNA synthetase in a non-human host cell, wherein said orthogonal tRNA synthetase preferentially aminoacylates said orthogonal tRNA with at least one non-naturally-encoded amino acid compared to a naturally-encoded amino acid by virtue of the orthogonal tRNA synthetase having a lower Km for the at least one non-naturally-encoded amino acid than for the naturally-encoded amino acid to thereby ribosomally incorporate said at least one non-naturally-encoded amino acid at selected positions into a 4HB polypeptide. Further provided are polypeptides produced by the method. (62) Divided Out of 548256

Troy E. Wilson

Papers

Modified Human Interferon Polypeptides and Their Uses

Biosynthetic polypeptides utilizing non-naturally encoded amino acids

Kinase inhibitors and methods of use

Modified Human Growth Hormone Polypeptides and Their Uses

Modified human four helical bundle polypeptides and their uses