Merck Sharp + Dohme Corp.

Celldex Therapeutics Limited

Glycofi, Incorporated

Celdara Medical, LLC

Terrance A Stadheim

Stefan Wildt

Piotr Bobrowicz

Stephen Robin Hamilton

Natarajan Sethuraman

Dongxing Zha

Liming Liu

Bianka Prinz

Tibor P Keler

Juergen Nett

Robert Davidson

Henry C Marsh

William James Cook

Byung-Kwon Choi

Michael A Meehl

Joana M Murad

Jake Reder

Li-Zhen He

Dongxin Zha

Sujatha Gomathinayagam

Huijuan Li

Piotri Bobrowicz

Robert C Davidson

Piotr Unit 9B Bobrowicz

The present invention is directed to methods and compositions for the production of Fc-containing polypeptides having improved properties and comprising mutations at positions 243 and 264 of the Fc region.

Fc-containing polypeptides having improved properties and comprising mutations at positions 243 and 264 of the Fc-region

The invention provides chimeric antigen receptors (CARs) that specifically bind to the T-cell immunoglobulin and mucin domain 1 (TIM-1) protein. The invention further relates to modified immune cells, e.g., T or NK cells, comprising such CARs, CAR-encoding nucleic acids, CAR-encoding vectors, and methods of making such compositions. The invention further relates to methods for therapeutic use of these CARs and modified immune cells for the treatment of a condition, disorder, or disease associated with cells expressing TIM-1 (e.g., cancer).

Chimeric antigen receptors targeting TIM-1

Method for preparing antibodies having improved properties

Lower eukaryotic host cells have been engineered to produce glycoprotein having at least one terminal &#x3b1;-galactosyl epitope. The glycoproteins are useful for the production of highly antigenic glycoprotein compositions with advantages for the production of vaccines.

Yeast strain for the production of proteins with terminal alpha-1,3-linked galactose

The present invention related to methods and compositions for producing therapeutic proteins in yeast cell lines, and in particular, lacking dipeptidyl aminopeptidase (DAP) activity. DAP activity has been eliminated by genetically modifying acell line such that STE13 and DAP2 have been deleted.

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Methods for producing proteins and glycoproteins inthat lack detectable cross binding activity to antibodies made against host cell antigens are described. In particular, methods are described wherein recombinantstrains that do not display a &#x3b2;-mannosyltransferase 2 activity with respect to an N-glycan or O-glycan and do not display at least one activity selected from a &#x3b2;-mannosyltransferase 1, 3, and 4 activity to produce recombinant proteins and glycoproteins. These recombinantstrains can produce proteins and glycoproteins that lack detectable &#x3b1;-mannosidase resistant &#x3b2;-mannose residues thereon and thus, lack cross binding activity to antibodies against host cell antigens. Further described are methods for producing bi-sialylated human erythropoietin inthat lack detectable cross binding activity to antibodies against host cell antigens.

Lower eukaryotic host cells have been recombinantly engineered to produce glycoprotein having human-like O-glycosylation. The glycoproteins are useful for the production of glycoprotein compositions with advantages for the production of human therapeutics.

Yeast strain for the production of proteins with modified O-glycosylation

Described is a method for increasing the N-glycosylation site occupancy of a therapeutic glycoprotein produced in recombinant host cells modified as described herein and genetically engineered to express the glycoprotein compared to the N-glycosylation site occupancy of the therapeutic glycoprotein produced in a recombinant host cell not modified as described herein. In particular, the method provides recombinant host cells that overexpress a heterologous single-subunit oligosaccharyltransferase, which in particular embodiments is capable of functionally suppressing the lethal phenotype of a mutation of at least one essential protein of the yeast oligosaccharyltransferase (OTase) complex, for example, theSTT3D protein, in the presence of expression of the host cell genes encoding the endogenous OTase complex. The method is useful for both producing therapeutic glycoproteins with increased N-glycosylation site occupancy in lower eukaryote cells such as yeast and filamentous fungi and in higher eukaryote cells such as plant and insect cells and mammalian cells.

The present invention relates to the elimination of mannosylphosphorylation on the glycans of glycoproteins in the yeast genus. The elimination of mannosylphosphorylated glycoproteins results from the disruption of the PNO1 gene and the newly isolatedMNN4B gene. The present invention further relates to methods for producing modified glycan structures in host cells that are free of glycan mannosylphosphorylation.

Methods for eliminating mannosylphosphorylation of glycans in the production of glycoproteins

Growing community of inventors

Lyme, NH, United States of America

Terrance A Stadheim