Patent classifications
C07K16/28
PROGRAMMED CELL DEATH RECEPTOR 1 ANTIBODY FORMULATION AND USE THEREOF
The present invention provides a pharmaceutical formulation containing an anti-PD-1 monoclonal antibody. The pharmaceutical formulation comprises an anti-PD-1 monoclonal antibody, a citrate-sodium citrate buffer solution, a protein protectant, a surfactant, and an isotonic regulator. The present invention also relates to an application of the pharmaceutical formulation in the preparation of a liquid formulation or lyophilized formulation for injection.
ANTIBODY CONSTRUCTS BINDING 4-1BB AND TUMOR-ASSOCIATED ANTIGENS AND USES THEREOF
- Daniel T. PATTON ,
- David M. MILLS ,
- Thomas Spreter Von Kreudenstein ,
- Gesa VOLKERS ,
- Dunja Urosev ,
- Lee FREIBURGER ,
- Zhuang DUAN ,
- Elizabeth HALVORSEN ,
- Harsh PRATAP ,
- Brandon CLAVETTE ,
- Anna Von Rossum ,
- Duncan BROWMAN ,
- Peter Wing Yiu CHAN ,
- Danny CHUI ,
- Robert William GENE ,
- Sylwia JANCOWSKI ,
- Sukhbir Singh KANG ,
- Patricia ZWIERZCHOWSKI
Described herein are antibody constructs comprising a 41-1BB binding domain and an antigen-binding domain that binds to a tumor-associated antigen (TAA), wherein the 4-1BB-binding domain and the TAA antigen-binding domain are linked directly or indirectly to a scaffold. The scaffold may be an Fc construct with modifications that reduce its ability to mediate effector function.
ANTIBODY CONSTRUCTS BINDING 4-1BB AND TUMOR-ASSOCIATED ANTIGENS AND USES THEREOF
- Daniel T. PATTON ,
- David M. MILLS ,
- Thomas Spreter Von Kreudenstein ,
- Gesa VOLKERS ,
- Dunja Urosev ,
- Lee FREIBURGER ,
- Zhuang DUAN ,
- Elizabeth HALVORSEN ,
- Harsh PRATAP ,
- Brandon CLAVETTE ,
- Anna Von Rossum ,
- Duncan BROWMAN ,
- Peter Wing Yiu CHAN ,
- Danny CHUI ,
- Robert William GENE ,
- Sylwia JANCOWSKI ,
- Sukhbir Singh KANG ,
- Patricia ZWIERZCHOWSKI
Described herein are antibody constructs comprising a 41-1BB binding domain and an antigen-binding domain that binds to a tumor-associated antigen (TAA), wherein the 4-1BB-binding domain and the TAA antigen-binding domain are linked directly or indirectly to a scaffold. The scaffold may be an Fc construct with modifications that reduce its ability to mediate effector function.
MODIFIED DOUBLE STRANDED OLIGONUCLEOTIDE
The disclosure is directed to dual variable domain immunoglobulin double-stranded RNA conjugates that are advantageous for inhibition of target gene expression, as well as compositions suitable for therapeutic use. The dual variable domain immunoglobulin comprises a first variable domain that binds to a binding target, and a second variable domain that comprises a reactive residue, where the linker is covalently conjugated to the reactive residue. The dsRNA is linked to the linker and is capable of inhibiting the expression of the target gene by RNA interference. The disclosure also provides pharmaceutical compositions comprising these conjugate and methods of inhibiting the expression of a target gene by administering these conjugates, e.g., for the treatment of various disease conditions.
Chemically Induced Association and Dissociation of Therapeutic FC Compositions and Chemically Induced Dimerization of T Cell Engager with Human Serum Albumin
The present disclosure provides a system that enables precise temporal control of the serum half-life a therapeutic moiety by inducing the association or disassociation of the therapeutic moiety with an Fc domain by a small molecule. The present disclosure also provides a system that enables precise control of the serum half- life a T cell engager domain by incorporating a chemically induced dimerizer (CID). One half of the CID is fused to a T cell engager, and the other half of the CID is fused to a HSA binding domain. Addition or removal of a small molecule induces association or dissociation of the T cell engager with HSA, thereby enabling precise temporal control of the serum half-life the T cell engager.
METHODS OF TREATING WARM AUTOIMMUNE HEMOLYTIC ANEMIA USING ANTI-FCRN ANTIBODIES
The present disclosure relates to compositions, methods, and uses for using an isolated anti-FcRn antibody or an antigen-binding fragment thereof that binds to neonatal Fc receptor (FcRn) to prevent, modulate, or treat warm autoimmune hemolytic anemia.
CHIMERIC ANTIGEN RECEPTORS AND RELATED METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER
Methods and compositions are provided related to therapeutic receptors, including chimeric antigen receptors (CARs), capable of specifically binding TYRP-1. The disclosed compositions include, for example, cells (e.g., immune cells) expressing TYRP-1 specific CARs, nucleic acids encoding TYRP-1 specific CARs, and TYRP-1 specific CAR polypeptides. Certain aspects relate to methods of treating cancer, including melanoma, using compositions comprising TYRP-1 specific CARs, for example cells expressing TYRP-1 specific CARs. In some embodiments, provided herein are chimeric polypeptides comprising a TYRP-1 binding domain, a hinge region, a transmembrane domain, and an intracellular signaling domain.
ANTI-BCMA/ANTI-4-1BB BISPECIFIC ANTIBODIES AND USES THEREOF
An anti-B-cell maturation antigen (BCMA)/anti-4-1BB bispecific antibody or an antigen-binding fragment thereof, and use thereof, are provided. The bispecific antibody or an antigen-binding fragment thereof may have high binding affinity to both of a BCMA protein and a 4-1BB protein and may be effectively used to prevent or treat a disease related to BCMA, 4-1BB, or both thereof (e.g., cancer).
BISPECIFIC ANTIBODIES AGAINST CHI3L1 AND CTLA4 WITH ENHANCED CYTOTOXIC EFFECTS ON TUMOR CELLS
Described herein are bispecific antibodies simultaneously targeting both CHI3L1 and the immune checkpoint molecule CTLA4. These antibodies manifest enhanced synergistic cytotoxic effects compared to the effects of individual CHI3L1 and CTLA4 antibodies, alone or in combination. Methods of treating tumors, including lung and brain tumors by administering the bispecific antibodies described herein are also provided.
NOVEL INTERLEUKIN-15 (IL-15) FUSION PROTEINS AND USES THEREOF
The present disclosure provides novel and improved IL-15 fusion proteins for use in the treatment of cancer and other disorders. In various embodiments, the fusion proteins of the invention have two functional domains: an IL-15/IL-15RαSushi domain (also referred to herein as an “IL-15/IL-15RαSushi complex”) and an antibody domain, each of which can take different forms, and configured such that the IL-15 is fused to the C-terminal of the antibody domain and co-expressed and non-covalently complexed with IL-15RαSushi. Importantly, the fusions proteins of the present invention address several of the limitations observed with the IL-15 therapeutics evaluated to date; specifically, the fusion proteins demonstrate extended the half-life of IL-15 in vivo, and demonstrate optimized preclinical activity compared to rIL-15 or related cytokine therapeutics.