WO2000042072A2 - Polypeptide variants with altered effector function - Google Patents
Polypeptide variants with altered effector function Download PDFInfo
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- WO2000042072A2 WO2000042072A2 PCT/US2000/000973 US0000973W WO0042072A2 WO 2000042072 A2 WO2000042072 A2 WO 2000042072A2 US 0000973 W US0000973 W US 0000973W WO 0042072 A2 WO0042072 A2 WO 0042072A2
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
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- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
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- C07K16/4283—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig
- C07K16/4291—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig against IgE
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- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
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- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/734—Complement-dependent cytotoxicity [CDC]
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- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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- C12N2799/00—Uses of viruses
- C12N2799/02—Uses of viruses as vector
- C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
- C12N2799/022—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from an adenovirus
Definitions
- the present invention concerns polypeptides comprising a variant Fc region. More particularly, the present invention concerns Fc region-containing polypeptides that have altered effector function as a consequence of one or more amino acid modifications in the Fc region thereof.
- Antibodies are proteins which exhibit binding specificity to a specific antigen.
- Native antibodies are usually heterotetrameric glycoproteins of about 150,000 daltons, composed of two identical light (L) chains and two identical heavy (H) chains. Each light chain is linked to a heavy chain by one covalent disuifide bond, while the number of disulfide linkages varies between the heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachai ⁇ disulfide bridges. Each heavy chain has at one end a variable domain (V H ) followed by a number of constant domains.
- V H variable domain
- Each light chain has a variable domain at one end (V L ) and a constant domain at its other end; the constant domain of the light chain is aligned with the first constant dprnain of the heavy chain, and the light chain variable domain is aligned with the variable domain'of the heavy chain. Particular amino acid residues are believed to form an interface between the light and heavy chain variable domains.
- the term "variable” refers to the fact that certain portions of the variable domains differ extensively in sequence among antibodies and are responsible for the binding specificity of each particular antibody for its particular antigen. However, the variability is not evenly distributed through the variable domains of antibodies. It is concentrated in three segments called complementarity determining regions (CDRs) both in the light chain and the heavy chain variable domains.
- CDRs complementarity determining regions
- variable domains The more highly conserved portions of the variable domains are called the framework regions (FRs).
- the variable domains of native heavy and light chains each comprise four FRs, largely adopting a ⁇ -sheet configuration, connected by three CDRs, which form loops connecting, and in some cases forming part of, the ⁇ -sheet structure.
- the CDRs in each chain are held together in close proximity by the FRs and, with the CDRs from the other chain, contribute to the formation of the antigen binding site of antibodies (see Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991 )).
- the constant domains are not involved directly in binding an antibody to an antigen, but exhibit various effector functions.
- antibodies or immunoglobulins can be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG and IgM, and several of these may be further divided into subclasses (isotypes), e.g. lgG1 , lgG2, lgG3, and lgG4; lgA1 and lgA2.
- the heavy chain constant regions that correspond to the different classes of immunoglobulins are called ⁇ , ⁇ , ⁇ , ⁇ , and ⁇ , respectively.
- human immunoglobulin classes only human lgG1 , lgG2, lgG3 and IgM are known to activate complement; and human lgG1 and lgG3 mediate ADCC more effectively than lgG2 and lgG4.
- FIG. 1 A schematic representation of the native lgG1 structure is shown in Fig. 1 , where the various portions of the native antibody molecule are indicated.
- Papain digestion of antibodies produces two identical antigen binding fragments, called Fab fragments, each with a single antigen binding site, and a residual "Fc" fragment, whose name reflects its ability to crystallize readily.
- the crystal structure of the human IgG Fc region has been determined (Deisenhofer, Biochemistry 20:2361-2370 (1981)).
- the Fc region is generated by papain cleavage N-terminal to Cys 226.
- the Fc region is central to the effector functions of antibodies.
- effector functions mediated by the antibody Fc region can be divided into two categories: (1 ) effector functions that operate after the binding of antibody to an antigen (these functions involve the participation of the complement cascade or Fc receptor (FcR)-bearing cells); and (2) effector functions that operate independently of antigen binding (these functions confer persistence in the circulation and the ability to be transferred across cellular barriers by transcytosis).
- (1 ) effector functions that operate after the binding of antibody to an antigen (these functions involve the participation of the complement cascade or Fc receptor (FcR)-bearing cells); and (2) effector functions that operate independently of antigen binding (these functions confer persistence in the circulation and the ability to be transferred across cellular barriers by transcytosis).
- FcR complement cascade or Fc receptor
- an antibody While binding of an antibody to the requisite antigen has a neutralizing effect that might prevent the binding of a foreign antigen to its endogenous target (e.g. receptor or ligand), binding alone may not remove the foreign antigen.
- an antibody To be efficient in removing and/or destructing foreign antigens, an antibody should be endowed with both high affinity binding to its antigen, and efficient effector functions.
- ADCC antibody-dependent cell-mediated cytotoxicity
- CDC complement dependent cytotoxicity
- Fc receptors which bind the Fc region of an antibody.
- FcRs are defined by their specificity for immunoglobulin isotypes; Fc receptors for IgG antibodies are referred to as Fc ⁇ R, for IgE as Fc ⁇ R, for IgA as Fc ⁇ R and so on.
- Fc ⁇ RI CD64
- Fc ⁇ RII CD32
- Fc ⁇ RIII CD16
- the three genes encoding the Fc ⁇ RI subclass are clustered in region 1q21.1 of the long arm of chromosome 1; the genes encoding Fc ⁇ RII isoforms (Fc ⁇ RIIA, Fc ⁇ RIIB and Fc ⁇ RIIC) and the two genes encoding Fc ⁇ RIII (Fc ⁇ RIIIA and Fc ⁇ RIIIB) are all clustered in region 1q22.
- Fc ⁇ RIIA, Fc ⁇ RIIB and Fc ⁇ RIIC the genes encoding Fc ⁇ RIII
- Fc ⁇ RIIIA and Fc ⁇ RIIIB are all clustered in region 1q22.
- Fc ⁇ RIIIB is found only on neutrophils
- Fc ⁇ RIIIA is found on macrophages, monocytes, natural killer (NK) cells, and a subpopulation of T-cells.
- Fc ⁇ RIIIA is the only FcR present on NK cells, one of the cell types implicated in ADCC.
- Fc ⁇ RI, Fc ⁇ RII and Fc ⁇ RIII are immunoglobulin superfamily (IgSF) receptors; Fc ⁇ RI has three IgSF domains in its extracellular domain, while Fc ⁇ RII and Fc ⁇ RIII have only two IgSF domains in their extracellular domains.
- IgSF immunoglobulin superfamily
- FcRn neonatal Fc receptor
- MHC major histocompatibility complex
- Pro331 in lgG3 was changed to Ser, and the affinity of this variant to target cells analyzed.
- the affinity was found to be six-fold lower than that of unmutated lgG3, indicating the involvement of Pro331 in Fc ⁇ RI binding.
- C1q is a hexavalent molecule with a molecular weight of approximately 460,000 and a structure likened to a bouquet of tulips in which six collagenous "stalks" are connected to six globular head regions.
- CDC complement dependent cytotoxicity
- the residue Pro331 has been implicated in C1q binding by analysis of the ability of human IgG subclasses to carry out complement mediated cell lysis. Mutation of Ser331 to Pro331 in lgG4 conferred the ability to activate complement. (Tao etal., J. Exp. Med., 178:661-667 (1993); Brekke et al., Eur. J. Immunol., 24:2542-47 (1994)).
- the present invention provides a variant of a parent polypeptide comprising an Fc region, which variant mediates antibody-dependent cell-mediated cytotoxicity (ADCC) in the presence of human effector cells more effectively, or binds an Fc gamma receptor (Fc ⁇ R) with better affinity, than the parent polypeptide and comprises at least one amino acid modification in the Fc region.
- the polypeptide variant may, for example, comprise an antibody or an immunoadhesin.
- the Fc region of the parent polypeptide preferably comprises a human Fc region; e.g., a human lgG1 , lgG2, lgG3 or lgG4 Fc region.
- the polypeptide variant preferably comprises an amino acid modification (e.g.
- the invention provides a polypeptide comprising a variant Fc region with altered Fc gamma receptor (Fc ⁇ R) binding affinity, which polypeptide comprises an amino acid modification at any one or more of amino acid positions 238, 239, 248, 249, 252, 254, 255, 256, 258, 265, 267, 268, 269, 270, 272, 276, 278, 280, 283, 285, 286, 289, 290, 292, 293, 294, 295, 296, 298, 301 , 303, 305, 307, 309, 312, 315, 320, 322, 324, 326, 327, 329, 330, 331, 333, 334, 335, 337, 338, 340, 360, 373, 376, 378, 382, 388, 389, 398, 414, 416, 419, 430, 434, 435, 437, 438 or 439 of the Fc region, wherein the numbering of the residues in the Fc region is that
- the variant Fc region preferably comprises a variant human IgG Fc region, e.g., a variant human lgG1, lgG2, lgG3 or lgG4 Fc region.
- a variant human IgG Fc region e.g., a variant human lgG1, lgG2, lgG3 or lgG4 Fc region.
- different residues from those identified herein were thought to impact FcR binding.
- IgG E318 was found to be important for binding (Lund et al. Molec. Immunol.
- the polypeptide variant with altered Fc ⁇ R binding activity displays reduced binding to an Fc ⁇ R and comprises an amino acid modification at any one or more of amino acid positions 238, 239, 248, 249, 252, 254, 265, 268, 269, 270, 272, 278, 289, 292, 293, 294, 295, 296, 298, 301 , 303, 322, 324, 327, 329, 333, 335, 338, 340, 373, 376, 382, 388, 389, 414, 416, 419, 434, 435, 437, 438 or 439 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat. WO 00/42072 PCT/TJSOO/00973
- the polypeptide variant may display reduced binding to an Fc ⁇ RI and comprise an amino acid modification at any one or more of amino acid positions 238, 265, 269, 270, 327 or 329 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
- the polypeptide variant may display reduced binding to an Fc ⁇ RII and comprise an amino acid modification at any one or more of amino acid positions 238, 265, 269, 270, 292, 294, 295, 298, 303, 324, 327, 329, 333, 335, 338, 373, 376, 414, 416, 419, 435, 438 or 439 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
- the polypeptide variant of interest may display reduced binding to an Fc ⁇ RIII and comprise an amino acid modification at one or more of amino acid positions 238, 239, 248, 249, 252, 254, 265, 268, 269, 270, 272, 278, 289, 293, 294, 295, 296, 301 , 303, 322, 327, 329, 338, 340, 373, 376, 382, 388, 389, 416, 434, 435 or 437 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
- the polypeptide variant with altered Fc ⁇ R binding affinity displays improved binding to the Fc ⁇ R and comprises an amino acid modification at any one or more of amino acid positions 255, 256, 258, 267, 268, 272, 276, 280, 283, 285, 286, 290, 298, 301, 305,
- polypeptide variant may display increased binding to an Fc ⁇ RIII and, optionally, may further display decreased binding to an Fc ⁇ RII.
- An exemplary such variant comprises amino acid modification(s) at position(s) 298 and/or 333 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
- the polypeptide variant may display increased binding to an Fc ⁇ RII and comprise an amino acid modification at any one or more of amino acid positions 255, 256, 258, 267, 268, 272, 276, 280, 283, 285, 286, 290, 301, 305, 307, 309, 312, 315, 320, 322, 326, 330, 331, 337, 340, 378, 398 or 430 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
- Such polypeptide variants with increased binding to an Fc ⁇ RII may optionally further display decreased binding to an Fc ⁇ RIII and may, for example, comprise an amino acid modification at any one or more of amino acid positions 268, 272, 298, 301 , 322 or 340 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
- the invention further provides a polypeptide comprising a variant Fc region with altered neonatal Fc receptor (FcRn) binding affinity, which polypeptide comprises an amino acid modification at any one or more of amino acid positions 238, 252, 253, 254, 255, 256, 265, 272, 286, 288, 303, 305, 307, 309, 311 , 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 386, 388, 400, 413, 415, 424, 433, 434, 435, 436, 439 or 447 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
- FcRn neonatal Fc receptor
- Such polypeptide variants with reduced binding to an FcRn may comprise an amino acid modification at any one or more of amino acid positions 252, 253, 254, 255, 288, 309, 386, 388, 400, 415, 433, 435, 436, 439 or 447 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
- polypeptide variants may, alternatively, display increased binding to FcRn and comprise an amino acid modification at any one or more of amino acid positions 238, 256, 265, 272, 286, 303, 305, 307, 311 , 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or 434 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.
- the invention also provides a composition comprising the polypeptide variant and a physiologically or pharmaceutically acceptable carrier or diluent.
- This composition for potential therapeutic use is sterile and may be lyophilized.
- the invention provides a method for determining the presence of an antigen of interest comprising exposing a sample suspected of containing the antigen to the polypeptide variant and determining binding of the polypeptide variant to the sample.
- the invention provides a method of treating a mammal suffering from or predisposed to a disease or disorder, comprising administering to the mammal a therapeutically effective amount of a polypeptide variant as disclosed herein, or of a composition comprising the polypeptide variant and a pharmaceutically acceptable carrier.
- the invention further provides: isolated nucleic acid encoding the polypeptide variant; a vector comprising the nucleic acid, optionally, operably linked to control sequences recognized by a host cell transformed with the vector; a host cell containing the vector; a method for producing the polypeptide variant comprising culturing this host cell so that the nucleic acid is expressed and, optionally, recovering the polypeptide variant from the host cell culture (e.g. from the host cell culture medium).
- the invention further provides a method for making a variant Fc region with altered Fc receptor (FcR) binding affinity, or altered antibody-dependent cell-mediated cytotoxicity (ADCC) activity, comprising:
- Step (b) of the method may comprise determining binding of the variant Fc region to one or more FcRs in vitro. Moreover, the method may result in the identification of a variant Fc region with improved FcR binding affinity, or with improved ADCC activity, in step (b) thereof.
- the FcR may, for example, be human Fc gamma receptor III (Fc ⁇ RIII).
- step (b) comprises determining binding of the variant Fc region to at least two different FcRs
- the FcRs tested preferably include human Fc gamma receptor II (FcyRII) and human Fc gamma receptor III (Fc ⁇ RIII).
- Figure 1 is a schematic representation of a native IgG. Disulfide bonds are represented by heavy lines between CH1 and CL domains and the two CH2 domains. V is variable domain; C is constant domain; L stands for light chain and H stands for heavy chain.
- Figure 2 shows C1q binding of wild type (wt) C2B8 antibody; C2B8 antibody with a human lgG2 constant region (lgG2); and variants K322A, K320A and E318A.
- Figure 3 depicts C1q binding of variants P331A, P329A and K322A.
- Figures 4A and 4B depict the amino acid sequences of E27 anti-lgE antibody light chain
- FIG. 4A SEQ ID NO: 1
- Fig. 4B heavy chain
- FIG. 5 is a schematic diagram of the "immune complex" prepared for use in the FcR assay described in Example 1.
- the hexamer comprising three anti-lgE antibody molecules (the "Fc region-containing polypeptide") and three IgE molecules (the “first target molecule") is shown.
- IgE has two "binding sites” for the anti-lgE antibody (E27) in the Fc region thereof.
- Each IgE molecule in the complex is further able to bind two VEGF molecules ("the second target polypeptide”).
- VEGF has two "binding sites” for IgE.
- Figure 6 shows C1q binding results obtained for variants D270K and D270V compared to wild type C2B8.
- Figure 7 depicts complement dependent cytotoxicity (CDC) of variants D270K and D270V, compared to wild type C2B8.
- Figure 8 shows C1q binding ELISA results for 293 cell-produced wild type C2B8 antibody (293-Wt-C2B8), CHO-produced wild type C2B8 antibody (CHO-Wt-C2B8) and various variant antibodies.
- Figure 9 shows C1q binding ELISA results obtained for wild type (wt) C2B8 and various variant antibodies as determined in Example 3.
- Figure 10 depicts the three-dimensional structure of a human IgG Fc region, highlighting residues: Asp270, Lys326, Pro329, Pro331 , Lys322 and Glu333.
- Figure 11 shows C1q binding ELISA results obtained for wild type C2B8 and various variant antibodies as determined in Example 3.
- WO 00/42072 PCT/TJSOO/00973
- Figure 12 shows C1q binding ELISA results obtained for wild type C2B8 and double variants, K326M-E333S and K326A-E333A.
- Figure 13 shows CDC of wild type C2B8 and double variants, K326M-E333S and K326A- E333A.
- Figure 14 depicts C1q binding ELISA results obtained for C2B8 with a human lgG4 (lgG4), wild type C2B8 (W.-C2B8), C2B8 with a human lgG2 constant region (lgG2), and variant antibodies as described in Example 3.
- Figures 15A and 15B show binding patterns for parent antibody (E27) to Fc ⁇ RIIB and Fc ⁇ RIIIA.
- Figure 15A shows the binding pattern for the humanized anti-lgE E27 lgG1 as a monomer (open circles), hexamer (closed squares), and immune complex consisting of multiple hexamers (closed triangles) to a recombinant GST fusion protein of the human FcyRIIB (CD32) receptor subunit.
- the hexameric complex (closed squares) was formed by the mixture of equal molar concentrations of E27 (which binds to the Fc region of human IgE) and a human myeloma IgE.
- the hexamer is a stable 1.1 kD complex consisting of 3 IgG molecules (150 kD each) and 3 IgE molecules (200 kD each).
- the immune complex (closed triangles) was formed sequentially by first mixing equal molar concentrations of E27 and recombinant anti-VEGF IgE (human IgE with Fab variable domains that bind human VEGF) to form the hexamer. Hexamers were then linked to form an immune complex by the addition of 2x molar concentration of human VEGF, a 44 kD homodimer which has two binding sites for the anti-VEGF IgE per mole of VEGF.
- Figure 15B shows the binding pattern to a recombinant GST fusion protein of the human Fc ⁇ RIIIA (CD16) receptor ⁇ subunit.
- Figure 16A shows the binding of immune complexes using different antigen-antibody pairs to recombinant GST fusion protein of the Fc ⁇ RIIA receptor ⁇ subunit.
- Figure 16B shows the binding of the same antigen-antibody pairs to the GST fusion protein of the Fc ⁇ RIIIA receptor subunit. Closed circles represent binding of human lgE:anti-lgE E27 lgG1 ; open circles represent binding of human VEGF:humanized anti-VEGF lgG1.
- Figure 17 summarizes differences in binding selectivity of some alanine variants between the different FCYRS. Binding of alanine variants at residues in the CH2 domain of anti-lgE E27 lgG1 are shown to Fc ⁇ RIIA, Fc ⁇ RIIB, and Fc ⁇ RIIIA. Type 1 abrogates binding to all three receptors: D278A (265 in EU numbering). Type 2 improves binding to Fc ⁇ RIIA and Fc ⁇ RIIB, while binding to Fc ⁇ RIIIA is unaffected: S280A (267 in EU numbering). Type 3 improves binding to Fc ⁇ RIIA and Fc ⁇ RIIB, but reduces binding to Fc ⁇ RIIIA: H281 A (268 in EU numbering).
- Type 4 reduces binding to Fc ⁇ RIIA and FcyRIIB, while improving binding to Fc ⁇ RIIIA: S317A (298 in EU numbering).
- Type 5 improves binding to Fc ⁇ RIIIA, but does not affect binding to Fc ⁇ RIIA and Fc ⁇ RIIB: E352A, K353A (333 and 334 in EU numbering).
- WO 00/42072 PCT/TJSOO/00973
- Figures 18A and 18B compare the Fc ⁇ RIIIA protein/protein assay and CHO GPI-Fc ⁇ RIIIA cell based assay, respectively.
- Figure 18A illustrates binding of selected alanine variants to Fc ⁇ RIIIA-GST fusion protein.
- S317A (298 in EU numbering) and S317A/K353A (298 and 334 in EU numbering) bind better than E27 wildtype, while D278A (265 in EU numbering) almost completely abrogates binding.
- Figure 18B illustrates that a similar pattern of binding is found on CHO cells expressing a recombinant GPI-linked form of Fc ⁇ RIIIA.
- Figures 19A and 19B compare the FcyRIIB protein/protein assay and CHO GPI-Fc ⁇ RIIB cell based assay, respectively.
- Figure 19A illustrates binding of selected alanine variants to
- Fc ⁇ RIIB-GST fusion protein H281 A (268 in EU numbering) binds better than E27 wildtype while S317A (298 in EU numbering) shows reduced binding.
- Figure 19B illustrates that a similar pattern of binding is found on CHO cells expressing a recombinant membrane bound form of FcyRIIB.
- Figure 20 shows single alanine substitutions in the CH2 domain of anti-HER2 lgG1
- HERCEPTIN® that influence Fc ⁇ RIIIA binding in both the protein-protein and cell-based assays alter the ability to bind to Fc ⁇ RIIIA on peripheral blood mononuclear cell (PBMC) effector cells.
- PBMC peripheral blood mononuclear cell
- Recombinant humanized anti-HER2 HERCEPTIN®
- 51cr-labeled SK-BR-3 cells was preincubated with 51cr-labeled SK-BR-3 cells for 30 minutes (opsonization) at 100 ng/ml (filled circles) and 1.25 ng/ml (filled squares). Keeping the SK-BR-3 tumor target cell concentration constant, the ratio of effector cells was increased from 0 to 100.
- the spontaneous cytotoxicity in the absence of antibody was 20% at an effectortarget (E:T) ratio of 100:1.
- E:T effectortarget
- a single alanine mutation that did not affect FcyRIIIA binding, variant G31 R309A (292 in EU numbering), did not effect ADCC (filled triangles).
- a single alanine mutation that only slightly increased binding to Fc ⁇ RIIIA, variant G30 K307A (290 in EU numbering), also showed slightly improved ADCC (i.e., a 1.1 fold improvement in ADCC activity, calculated as area under the curve) at 1.25 ng/ml at all E:T ratios (filled diamonds) compared to wildtype antibody at 1.25 ng/ml (filled square).
- a single alanine mutation that decreased binding to Fc ⁇ RIIIA, variant G34 Q312A (295 in EU numbering), also showed decreased ADCC activity (filled inverted triangles).
- Figure 22A depicts alignments of native sequence IgG Fc regions.
- humlgGI non-A and A allotypes
- humlgG2 SEQ ID NO:5
- humlgG3 SEQ ID NO:6
- humlgG4 SEQ ID NO:7
- the human lgG1 sequence is the non-A allotype, and differences between this sequence and the A allotype (at positions 356 and 358; EU numbering system) are shown below the human lgG1 sequence.
- FIG. 22A shows percent identity among the Fc region sequences of Figure 22A.
- Figure 23 depicts alignments of native sequence human IgG Fc region sequences, humlgGI (non-A and A allotypes; SEQ ID NOs:3 and 4, respectively), humlgG2 (SEQ ID NO:5), humlgG3 (SEQ ID NO:6) and humlgG4 (SEQ ID NO:7) with differences between the sequences marked with asterisks.
- Figure 24 shows area under curve (AUC) for selected variants compared to anti-HER2 lgG1 (HERCEPTIN ® ) in a 4 hour ADCC assay.
- Variant G36 (S317A; 298 in Eu numbering) with improved binding to Fc ⁇ RIIIA showed improved ADCC activity; variant G31 (R309A; 292 in Eu numbering) which did not display altered Fc ⁇ RIIIA binding, also had unaltered ADCC activity; and G14 (D265A; 278 in Eu numbering) which had reduced Fc ⁇ RIIIA binding, also had reduced ADCC activity.
- the numbering of the residues in an immunoglobulin heavy chain is that of the EU index as in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (1991), expressly incorporated herein by reference.
- the "EU index as in Kabat” refers to the residue numbering of the human lgG1 EU antibody.
- a "parent polypeptide” is a polypeptide comprising an amino acid sequence which lacks one or more of the Fc region modifications disclosed herein and which differs in effector function compared to a polypeptide variant as herein disclosed.
- the parent polypeptide may comprise a native sequence Fc region or an Fc region with pre-existing amino acid sequence modifications (such as additions, deletions and/or substitutions).
- Fc region is used to define a C-terminal region of an immunoglobulin heavy chain, e.g., as shown in Figure 1.
- the "Fc region” may be a native sequence Fc region or a variant Fc region.
- the human IgG heavy chain Fc region is usually defined to stretch from an amino acid WO 00/42072 PCT/TJSOO/00973
- the Fc region of an immunoglobulin generally comprises two constant domains, CH2 and CH3, as shown, for example, in Fig. 1.
- the "CH2 domain” of a human IgG Fc region usually extends from about amino acid 231 to about amino acid 340.
- the CH2 domain is unique in that it is not closely paired with another domain. Rather, two N-linked branched carbohydrate chains are interposed between the two CH2 domains of an intact native IgG molecule. It has been speculated that the carbohydrate may provide a substitute for the domain-domain pairing and help stabilize the CH2 domain.
- the "CH3 domain” comprises the stretch of residues C-terminal to a CH2 domain in an
- Fc region i.e. from about amino acid residue 341 to about amino acid residue 447 of an IgG
- a “functional Fc region” possesses an “effector function” of a native sequence Fc region.
- effector functions include C1q binding; complement dependent cytotoxicity; Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g. B cell receptor; BCR), etc.
- ADCC antibody-dependent cell-mediated cytotoxicity
- phagocytosis down regulation of cell surface receptors (e.g. B cell receptor; BCR), etc.
- Such effector functions generally require the Fc region to be combined with a binding domain (e.g. an antibody variable domain) and can be assessed using various assays as herein disclosed, for example.
- a “native sequence Fc region” comprises an amino acid sequence identical to the amino acid sequence of an Fc region found in nature.
- Native sequence human Fc regions are shown in Fig. 23 and include a native sequence human IgGI Fc region (non-A and A allotypes); native sequence human lgG2 Fc region; native sequence human lgG3 Fc region; and native sequence human lgG4 Fc region as well as naturally occurring variants thereof.
- Native sequence murine Fc regions are shown in Fig. 22A.
- a “variant Fc region” comprises an amino acid sequence which differs from that of a native sequence Fc region by virtue of at least one "amino acid modification" as herein defined.
- the variant Fc region has at least one amino acid substitution compared to a native sequence Fc region or to the Fc region of a parent polypeptide, e.g. from about one to about ten amino acid substitutions, and preferably from about one to about five amino acid substitutions in a native sequence Fc region or in the Fc region of the parent polypeptide.
- the variant Fc region herein will preferably possess at least about 80% homology with a native sequence Fc region and/or with an Fc region of a parent polypeptide, and most preferably at least about 90% homology therewith, more preferably at least about 95% homology therewith.
- Homology is defined as the percentage of residues in the amino acid sequence variant that are identical after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent homology. Methods and computer programs for the alignment are well known in the art. One such computer program is "Align 2", authored by Genentech, Inc., which was filed with user documentation in the United States Copyright Office, Washington, DC 20559, on December 10, 1991.
- Fc region-containing polypeptide refers to a polypeptide, such as an antibody or immunoadhesin (see definitions below), which comprises an Fc region.
- Fc receptor or “FcR” are used to describe a receptor that binds to the Fc region of an antibody.
- the preferred FcR is a native sequence human FcR.
- a preferred FcR is one which binds an IgG antibody (a gamma receptor) and includes receptors of the Fc ⁇ RI, Fc ⁇ RII, and Fc ⁇ RIII subclasses, including allelic variants and alternatively spliced forms of these receptors.
- Fc ⁇ RII receptors include Fc ⁇ RIIA (an “activating receptor") and Fc ⁇ RIIB (an “inhibiting receptor”), which have similar amino acid sequences that differ primarily in the cytoplasmic domains thereof.
- Activating receptor Fc ⁇ RIIA contains an immunoreceptor tyrosine- based activation motif (ITAM) in its cytoplasmic domain.
- Inhibiting receptor Fc ⁇ RIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic domain, (see review M. in Daeron, Annu. Rev. Immunol. 15:203-234 (1997)).
- FcRs are reviewed in Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991 ); Capel etal., Imm ⁇ nomethods 4:25-34 (1994); and de Haas et al., J. Lab. Clin. Med. 126:330-41 (1995).
- FcR FcR
- FcRn neonatal receptor
- Antibody-dependent cell-mediated cytotoxicity and “ADCC” refer to a cell-mediated reaction in which nonspecific cytotoxic cells that express FcRs (e.g. Natural Killer (NK) cells, neutrophils, and macrophages) recognize bound antibody on a target ceil and subsequently cause lysis of the target cell.
- FcRs e.g. Natural Killer (NK) cells, neutrophils, and macrophages
- the primary cells for mediating ADCC NK cells, express Fc ⁇ RIII only, whereas monocytes express Fc ⁇ RI, Fc ⁇ RII and Fc ⁇ RIII.
- FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991 ).
- Human effector cells are leukocytes which express one or more FcRs and perform effector functions. Preferably, the cells express at least Fc ⁇ RIII and perform ADCC effector function. Examples of human leukocytes which mediate ADCC include peripheral blood mononuclear cells (PBMC), natural killer (NK) cells, monocytes, cytotoxic T cells and neutrophils; with PBMCs and NK cells being preferred.
- PBMC peripheral blood mononuclear cells
- NK natural killer cells
- monocytes cytotoxic T cells and neutrophils
- the effector cells may be isolated from a native source thereof, e.g. from blood or PBMCs as described herein.
- a polypeptide variant with "altered” FcR binding affinity or ADCC activity is one which has either enhanced or diminished FcR binding activity and/or ADCC activity compared to a parent polypeptide or to a polypeptide comprising a native sequence Fc region.
- the polypeptide variant which "displays increased binding" to an FcR binds at least one FcR with better affinity than the parent polypeptide.
- the polypeptide variant which "displays decreased binding" to an FcR binds at least one FcR with worse affinity than a parent polypeptide.
- Such variants which display decreased binding to an FcR may possess little or no appreciable binding to an FcR, e.g., 0-20% binding to the FcR compared to a native sequence IgG Fc region, e.g. as determined in the Examples herein.
- the polypeptide variant which binds an FcR with "better affinity" than a parent polypeptide is one which binds any one or more of the above identified FcRs with substantially better binding affinity than the parent antibody, when the amounts of polypeptide variant and parent polypeptide in the binding assay are essentially the same.
- the polypeptide variant with improved FcR binding affinity may display from about 1.15 fold to about 100 fold, e.g. from about 1.2 fold to about 50 fold improvement in FcR binding affinity compared to the parent polypeptide, where FcR binding affinity is determined, for example, as disclosed in the Examples herein.
- ADCC in the presence of human effector cells more effectively than a parent antibody
- ADCC in vitro or in vivo is substantially more effective at mediating ADCC, when the amounts of polypeptide variant and parent antibody used in the assay are essentially the same.
- such variants will be identified using the in vitro ADCC assay as herein disclosed, but other assays or methods for determining ADCC activity, e.g. in an animal model etc, are contemplated.
- the preferred variant is from about 1.5 fold to about 100 fold, e.g. from about two fold to about fifty fold, more effective at mediating ADCC than the parent, e.g. in the in vitro assay disclosed herein.
- amino acid modification refers to a change in the amino acid sequence of a predetermined amino acid sequence.
- exemplary modifications include an amino acid substitution, insertion and/or deletion.
- the preferred amino acid modification herein is a substitution.
- amino acid modification at a specified position, e.g. of the Fc region, refers to the substitution or deletion of the specified residue, or the insertion of at least one amino acid residue adjacent the specified residue.
- insertion "adjacent" a specified residue is meant insertion within one to two residues thereof. The insertion may be N-terminal or C-terminal to the specified residue.
- amino acid substitution refers to the replacement of at least one existing amino acid residue in a predetermined amino acid sequence with another different “replacement” amino acid residue.
- the replacement residue or residues may be "naturally occurring amino acid residues" (i.e. encoded by the genetic code) and selected from the group consisting of: alanine (Ala); arginine (Arg); asparagine (Asn); aspartic acid (Asp); cysteine (Cys); glutamine (Gin); glutamic acid (Glu); glycine (Gly); histidine (His); isoleucine (lie): leucine (Leu); lysine (Lys); methionine (Met); phenylalanine (Phe); praline (Pro); serine (Ser); threonine (Thr); tryptophan (Trp); tyrosine (Tyr); and valine (Val).
- the replacement residue is not cysteine.
- substitution with one or more non-naturally occurring amino acid residues is also encompassed by the definition of an amino acid substitution herein.
- a "non-naturally occurring amino acid residue” refers to a residue, other than those naturally occurring amino acid residues listed above, which is able to covalently bind adjacent amino acid residues(s) in a polypeptide chain. Examples of non-naturally occu ⁇ ing amino acid residues include norleucine, ornithine, norvaline, homoserine and other amino acid residue analogues such as those described in Ellman et al. Meth. Enzym. 202:301-336 (1991 ).
- amino acid insertion refers to the incorporation of at least one amino acid into a predetermined amino acid sequence. While the insertion will usually consist of the insertion of one or two amino acid residues, the present application contemplates larger "peptide insertions", e.g. insertion of about three to about five or even up to about ten amino acid residues. The inserted residue(s) may be naturally occurring or non-naturally occurring as disclosed above.
- amino acid deletion refers to the removal of at least one amino acid residue from a predetermined amino acid sequence.
- Hinge region is generally defined as stretching from Glu216 to Pro230 of human IgGI (Burton, Molec. //n/nu >/.22:161-206 (1985)). Hinge regions of other IgG isotypes may be aligned with the IgGI sequence by placing the first and last cysteine residues forming inter-heavy chain S-S bonds in the same positions.
- the "lower hinge region" of an Fc region is normally defined as the stretch of residues immediately C-terminal to the hinge region, i.e. residues 233 to 239 of the Fc region. Prior to the present invention, Fc ⁇ R binding was generally attributed to amino acid residues in the lower hinge region of an IgG Fc region.
- C1q is a polypeptide that includes a binding site for the Fc region of an immunoglobulin.
- C1q together with two serine proteases, Clr and C1s, forms the complex C1, the first component of the complement dependent cytotoxicity (CDC) pathway.
- Human C1q can be purchased commercially from, e.g. Quidel, San Diego, CA.
- binding domain refers to the region of a polypeptide that binds to another molecule.
- the binding domain can comprise a portion of a polypeptide WO 00/42072 PCT/TJSOO/00973
- One useful binding domain is the extracellular domain of an FcR ⁇ chain.
- antibody is used in the broadest sense and specifically covers monoclonal antibodies (including full length monoclonal antibodies), polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments so long as they exhibit the desired biological activity.
- Antibody fragments comprise a portion of an intact antibody, generally including the antigen binding or variable region of the intact antibody or the Fc region of an antibody which retains FcR binding capability.
- antibody fragments include linear antibodies; single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.
- the antibody fragments preferably retain at least part of the hinge and optionally the CH1 region of an IgG heavy chain. More preferably, the antibody fragments retain the entire constant region of an IgG heavy chain, and include an IgG light chain.
- the term "monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to conventional (polyclonal) antibody preparations that typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen.
- the modifier "monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method.
- the monoclonal antibodies to be used in accordance with the present invention may be made by the hybridoma method first described by Kohler et al., Nature 256:495 (1975), or may be made by recombinant DNA methods (see, e.g., U.S. Patent No. 4,816,567).
- the "monoclonal antibodies” may also be isolated from phage antibody libraries using the techniques described in Clackson etal., Nature 352:624-628 (1991) and Marks et al., J. Mol. Biol. 222:581-597 (1991 ), for example.
- the monoclonal antibodies herein specifically include "chimeric" antibodies (immunoglobulins) in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such WO 00/42072 PCT/TJSOO/00973
- Humanized forms of non-human (e.g., murine) antibodies are chimeric antibodies that contain minimal sequence derived from non-human immunoglobulin.
- humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a hypervariable region of the recipient are replaced by residues from a hypervariable region of a non-human species (donor antibody) such as mouse, rat, rabbit or nonhuman primate having the desired specificity, affinity, and capacity.
- donor antibody such as mouse, rat, rabbit or nonhuman primate having the desired specificity, affinity, and capacity.
- Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues.
- humanized antibodies may comprise residues that are not found in the recipient antibody or in the donor antibody. These modifications are made to further refine antibody performance.
- the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which ail or substantially all of the hypervariable loops correspond to those of a non- human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin sequence.
- the humanized antibody optionally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin.
- Fc immunoglobulin constant region
- hypervariable region when used herein refers to the amino acid residues of an antibody which are responsible for antigen-binding.
- the hypervariable region comprises amino acid residues from a "complementarity determining region" or "CDR" (i.e. residues 24-34 (L1), 50- 56 (L2) and 89-97 (L3) in the light chain variable domain and 31-35 (H1 ), 50-65 (H2) and 95-102 (H3) in the heavy chain variable domain; Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)) and/or those residues from a "hypervariable loop" (i.e.
- “Framework” or "FR” residues are those variable domain residues other than the hypervariable region residues as herein defined.
- immunoadhesin designates antibody-like molecules which combine the "binding domain" of a heterologous "adhesin” protein (e.g. a receptor, ligand or enzyme) with an immunoglobulin constant domain.
- the immunoadhesins comprise a fusion of the adhesin amino acid sequence with the desired binding specificity which is other than the antigen recognition and binding site (antigen combining site) of an antibody (i.e. is "heterologous") and an immunoglobulin constant domain sequence.
- ligand binding domain refers to any native cell-surface receptor or any region or derivative thereof retaining at least a qualitative ligand binding ability of a corresponding native receptor.
- the receptor is from a cell-surface polypeptide having an extracellular domain that is homologous to a member of the immunoglobulin supergenefamily.
- Other receptors which are not members of the immunoglobulin supergenefamily but are nonetheless specifically covered by this definition, are receptors for cytokines, and in particular receptors with tyrosine kinase activity (receptor tyrosine kinases), members of the hematopoietin and nerve growth factor receptor superfamilies, and cell adhesion molecules, e.g.
- receptor binding domain is used to designate any native ligand for a receptor, including cell adhesion molecules, or any region or derivative of such native ligand retaining at least a qualitative receptor binding ability of a corresponding native ligand. This definition, among others, specifically includes binding sequences from ligands for the above-mentioned receptors.
- an "antibody-immunoadhesin chimera” comprises a molecule that combines at least one binding domain of an antibody (as herein defined) with at least one immunoadhesin (as defined in this application).
- Exemplary antibody-immunoadhesin chimeras are the bispecific CD4-lgG chimeras described in Berg et al., PNAS (USA) 88:4723-4727 (1991) and Chamow et al., J. Immunol. 153:4268 (1994).
- an "isolated" polypeptide is one that has been identified and separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials that would interfere with diagnostic or therapeutic uses for the polypeptide, and may include enzymes, hormones, and other proteinaceous or nonproteinaceous solutes.
- the polypeptide will be purified (1) to greater than 95% by weight of polypeptide as determined by the Lowry method, and most preferably more than 99% by weight, (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under reducing or nonreducing conditions using Coomassie blue or, preferably, silver stain.
- Isolated polypeptide includes the polypeptide in situ within recombinant cells since at least one component of the polypeptide's natural environment will not be present. Ordinarily, however, isolated polypeptide will be prepared by at least one purification step.
- Treatment refers to both therapeutic treatment and prophylactic or preventative measures. Those in need of treatment include those already with the disorder as well as those in which the disorder is to be prevented.
- a “disorder” is any condition that would benefit from treatment with the polypeptide variant. This includes chronic and acute disorders or diseases including those pathological conditions WO 00/42072 PCT/TJSOO/00973
- the disorder is cancer.
- cancer and “cancerous” refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth.
- Examples of cancer include but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia.
- cancers include squamous cell cancer, small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, squamous carcinoma of the lung, cancer of the peritoneum, hepatocelluiar cancer, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma and various types of head and neck cancer.
- a "HER2-expressing cancer” is one comprising cells which have HER2 receptor protein (Semba et al., PNAS (USA) 82:6497-6501 (1985) and Yamamoto et al. Nature 319:230-234 (1986) (Genebank accession number X03363)) present at their cell surface, such that an anti- HER2 antibody is able to bind to the cancer.
- label when used herein refers to a detectable compound or composition which is conjugated directly or indirectly to the polypeptide.
- the label may be itself be detectable (e.g., radioisotope labels or fluorescent labels) or, in the case of an enzymatic label, may catalyze chemical alteration of a substrate compound or composition which is detectable.
- an "isolated" nucleic acid molecule is a nucleic acid molecule that is identified and separated from at least one contaminant nucleic acid molecule with which it is ordinarily associated in the natural source of the polypeptide nucleic acid.
- An isolated nucleic acid molecule is other than in the form or setting in which it is found in nature. Isolated nucleic acid molecules therefore are distinguished from the nucleic acid molecule as it exists in natural cells.
- an isolated nucleic acid molecule includes a nucleic acid molecule contained in cells that ordinarily express the polypeptide where, for example, the nucleic acid molecule is in a chromosomal location different from that of natural cells.
- control sequences refers to DNA sequences necessary for the expression of an operably linked coding sequence in a particular host organism.
- the control sequences that are suitable for prokaryotes include a promoter, optionally an operator sequence, and a ribosome binding site.
- Eukaryotic cells are known to utilize promoters, polyadenylation signals, and enhancers.
- Nucleic acid is "operably linked" when it is placed into a functional relationship with another nucleic acid sequence.
- DNA for a presequence or secretory leader is WO 00/42072 PCT/TJSOO/00973
- operably linked means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Linking is accomplished by ligation at convenient restriction sites.
- the synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice.
- the expressions "cell,” “cell line,” and “cell culture” are used interchangeably and all such designations include progeny.
- the words “transfo ⁇ nants” and “transformed cells” include the primary subject cell and cultures derived therefrom without regard for the number of transfers. It is also understood that all progeny may not be precisely identical in DNA content, due to deliberate or inadvertent mutations. Mutant progeny that have the same function or biological activity as screened for in the originally transformed cell are included. Where distinct designations are intended, it will be clear from the context.
- molecular complex when used herein refers to the relatively stable structure which forms when two or more heterologous molecules (e.g. polypeptides) bind (preferably noncovalently) to one another.
- heterologous molecules e.g. polypeptides
- the preferred molecular complex herein is an immune complex.
- Immuno complex refers to the relatively stable structure which forms when at least one target molecule and at least one heterologous Fc region-containing polypeptide bind to one another forming a larger molecular weight complex.
- immune complexes are antigen- antibody aggregates and target molecule-immunoadhesin aggregates.
- target molecule refers to a molecule, usually a polypeptide, which is capable of being bound by a heterologous molecule and has one or more binding sites for the heterologous molecule.
- binding site refers to a region of a molecule to which another molecule can bind.
- first target molecule herein comprises at least two distinct binding sites (for example, two to five separate binding sites) for an analyte (e.g. an Fc region-containing polypeptide) such that at least two analyte molecules can bind to the first target molecule.
- the two or more binding sites are identical (e.g. having the same amino acid sequence, where the target molecule is a polypeptide).
- Example 1 the first target molecule was IgE and had two separate binding sites in the Fc region thereof to which the Fc region-containing polypeptide (an anti-lgE antibody, E27) could bind.
- target molecules include dimers of substantially identical monomors (e.g. neurotrophins, IL8 and VEGF) or are polypeptides comprising two or more substantially identical polypeptide chains (e.g. antibodies or immunoadhesins).
- the "second target molecule” comprises at least two distinct binding sites (for example, two to five separate binding sites) for the first target molecule such that at least two first target molecules can bind to the second target molecule.
- the two or more binding sites are identical (e.g. having the same amino acid sequence, where the target molecule is a polypeptide).
- the second target molecule was VEGF, which has a pair of distinct binding sites to which the variable domain of the IgE antibody could bind.
- second target molecules are contemplated, e.g. other dimers of substantially identical monomers (e.g. neurotrophins or IL8) or polypeptides comprising two or more substantially identical domains (e.g. antibodies or immunoadhesins).
- substantially identical monomers e.g. neurotrophins or IL8
- polypeptides comprising two or more substantially identical domains (e.g. antibodies or immunoadhesins).
- an "analyte” is a substance that is to be analyzed.
- the preferred analyte is an Fc region- containing polypeptide that is to be analyzed for its ability to bind to an Fc receptor.
- a "receptor” is a polypeptide capable of binding at least one ligand.
- the preferred receptor is a cell-surface receptor having an extracellular ligand-binding domain and, optionally, other domains (e.g. transmembrane domain, intracellular domain and/or membrane anchor).
- the receptor to be evaluated in the assay described herein may be an intact receptor or a fragment or derivative thereof (e.g. a fusion protein comprising the binding domain of the receptor fused to one or more heterologous polypeptides).
- the receptor to be evaluated for its binding properties may be present in a cell or isolated and optionally coated on an assay plate or some other solid phase.
- low affinity receptor denotes a receptor that has a weak binding affinity for a ligand of interest, e.g. having a binding constant of about 50nM or worse affinity.
- exemplary low affinity receptors include Fc ⁇ RII and Fc ⁇ RIII. II. Modes for Carrying Out the Invention
- the invention herein relates to a method for making a polypeptide variant.
- the "parent”, “starting” or “nonvariant” polypeptide is prepared using techniques available in the art for generating polypeptides comprising an Fc region.
- the parent polypeptide is an antibody and exemplary methods for generating antibodies are described in more detail in the following sections.
- the parent polypeptide may, however, be any other polypeptide comprising an Fc region, e.g. an immunoadhesin. Methods for making immunoadhesins are elaborated in more detail hereinbelow.
- a variant Fc region may be generated according to the methods herein disclosed and this "variant Fc region" can be fused to a heterologous polypeptide of choice, such as an antibody variable domain or binding domain of a receptor or ligand.
- a heterologous polypeptide of choice such as an antibody variable domain or binding domain of a receptor or ligand.
- the parent polypeptide comprises an Fc region.
- the Fc region of the parent polypeptide will comprise a native sequence Fc region, and preferably a human native sequence Fc region.
- the Fc region of the parent polypeptide may have one or more pre-existing amino acid sequence alterations or modifications from a native sequence Fc region.
- the C1q binding activity of the Fc region may have been previously altered (other types of Fc region modifications are described in more detail below).
- the parent polypeptide Fc region is "conceptual" and, while it does not physically exist, the antibody engineer may decide upon a desired variant Fc region amino acid sequence and generate a polypeptide comprising that sequence or a DNA encoding the desired variant Fc region amino acid sequence.
- a nucleic acid encoding an Fc region of a parent polypeptide is available and this nucleic acid sequence is altered to generate a variant nucleic acid sequence encoding the Fc region variant.
- DNA encoding an amino acid sequence variant of the starting polypeptide is prepared by a variety of methods known in the art. These methods include, but are not limited to, preparation by site-directed (or oligonucleotide-mediated) mutagenesis, PCR mutagenesis, and cassette mutagenesis of an earlier prepared DNA encoding the polypeptide
- Site-directed mutagenesis is a preferred method for preparing substitution variants. This technique is well known in the art (see, e.g.,Carter et al. Nucleic Acids Res. 13:4431-4443 (1985) and Kunkel etal., Proc. Natl. Acad.Sci.USA 82:488 (1987)). Briefly, in carrying out site- directed mutagenesis of DNA, the starting DNA is altered by first hybridizing an oligonucleotide encoding the desired mutation to a single strand of such starting DNA.
- a DNA polymerase is used to synthesize an entire second strand, using the hybridized oligonucleotide as a primer, and using the single strand of the starting DNA as a template.
- the oligonucleotide encoding the desired mutation is incorporated in the resulting double-stranded DNA.
- PCR mutagenesis is also suitable for making amino acid sequence variants of the starting polypeptide. See Higuchi, in PCR Protocols, pp.177-183 (Academic Press, 1990); and Vallette etal., Nuc. Acids Res. 17:723-733 (1989). Briefly, when small amounts of template DNA are used as starting material in a PCR, primers that differ slightly in sequence from the corresponding region in a template DNA can be used to generate relatively large quantities of a specific DNA fragment that differs from the template sequence only at the positions where the primers differ from the template.
- the starting material is the plasmid (or other vector) comprising the starting polypeptide DNA to be mutated.
- the codon(s) in the starting DNA WO 00/42072 PCT/TJSOO/00973
- the plasmid DNA is cut at these sites to linearize it.
- a double-stranded oligonucleotide encoding the sequence of the DNA between the restriction sites but containing the desired mutation(s) is synthesized using standard procedures, wherein the two strands of the oligonucleotide are synthesized separately and then hybridized together using standard techniques.
- This double-stranded oligonucleotide is referred to as the cassette.
- This cassette is designed to have 5' and 3' ends that are compatible with the ends of the linearized plasmid, such that it can be directly ligated to the plasmid.
- This plasmid now contains the mutated DNA sequence.
- the desired amino acid sequence encoding a polypeptide variant can be determined, and a nucleic acid sequence encoding such amino acid sequence variant can be generated synthetically.
- the amino acid sequence of the parent polypeptide is modified in order to generate a variant Fc region with altered Fc receptor binding affinity or activity in vitro and/or in vivo and/or altered antibody-dependent cell-mediated cytotoxicity (ADCC) activity in vitro and/or in vivo.
- ADCC antibody-dependent cell-mediated cytotoxicity
- the modification entails one or more amino acid substitutions.
- the replacement residue does not correspond to a residue present in the same position in any of the native sequence Fc regions in Figure 22A.
- Pro331 of a human lgG3 or IgGI Fc region is replaced with a residue other than Ser (the corresponding aligned residue found in native sequence human lgG4).
- the residue in the parent polypeptide which is substituted with a replacement residue is not an alanine and/or is not residue AIa339 of an Fc region.
- an amino acid substitution preferably the residue in the parent polypeptide is replaced with an alanine residue.
- the present invention contemplates replacement of the residue of the parent polypeptide with any other amino acid residue.
- the substitution may, for example, be a "conservative substitution”. Such conservative substitutions are shown in Table 1 under the heading of "preferred substitution”. More substantial changes may be achieved by making one or more "exemplary substitutions" which are not the preferred substitution in Table 1.
- Substantial modifications in the biological properties of the Fc region may be accomplished by selecting substitutions that differ significantly in their effect on maintaining (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a sheet or helical conformation, (b) the charge or hydrophobicity of the molecule at the target site, or (c) the bulk of the side chain.
- Naturally occu ⁇ ing residues are divided into groups based on common side-chain properties:
- hydrophobic norleucine, met, ala, val, leu, ile
- Non-conservative substitutions will entail exchanging a member of one of these classes for a member of another class.
- Conservative and non-conservative amino acid substitutions are exemplified in Table 8 hereinbelow.
- Example 4 one can engineer an Fc region variant with altered binding affinity for one or more FcRs.
- different classes of Fc region variants can be made e.g.. as summarized in the following table. Where the variant Fc region has more than one amino acid substitution, generally, but not necessarily, amino acid substitutions in the same class are combined to achieve the desired result.
- the present invention contemplates other modifications of the parent Fc region amino acid sequence in order to generate an Fc region variant with altered effector function.
- One may, for example, delete one or more amino acid residues of the Fc region in order to reduce binding to an FcR.
- one will delete one or more of the Fc region residues identified herein as effecting FcR binding (see Example 4 below) in order to generate such an Fc region variant.
- no more than one to about ten Fc region residues will be deleted according to this embodiment of the invention.
- the Fc region herein comprising one or more amino acid deletions will preferably retain at least about 80%, and preferably at least about 90%, and most preferably at least about 95%, of the parent Fc region or of a native sequence human Fc region.
- the parent polypeptide Fc region is a human Fc region, e.g. a native sequence human Fc region human IgGI (A and non-A allotypes), lgG2, lgG3 or lgG4 Fc region. Such sequences are shown in Fig. 23.
- the parent polypeptide preferably has pre-existing ADCC activity, e.g., it comprises a human IgGI or human lgG3 Fc region.
- the variant with improved ADCC mediates ADCC substantially more effectively than WO 00/42072 PCT/TJSOO/00973
- the variant comprises, or consists essentially of, substitutions of two or three of the residues at positions 298, 333 and 334 of the Fc region. Most preferably, residues at positions 298, 333 and 334 are substituted, (e.g. with alanine residues).
- residues at positions 298, 333 and 334 are substituted, (e.g. with alanine residues).
- an Fc region variant with improved binding affinity for Fc ⁇ RIII which is thought to be an important FcR for mediating ADCC. For example, one may introduce an amino acid modification (e.g.
- the variant with improved binding affinity for Fc ⁇ RIII may further have reduced binding affinity for Fc ⁇ RII, especially reduced affinity for the inhibiting Fc ⁇ RIIB receptor.
- the amino acid modif ⁇ cation(s) are preferably introduced into the CH2 domain of a Fc region, since the experiments herein indicate that the CH2 domain is important for FcR binding activity. Moreover, unlike the teachings of the above-cited art, the instant application contemplates the introduction of a modification into a part of the Fc region other than in the lower hinge region thereof.
- Useful amino acid positions for modification in order to generate a variant IgG Fc region with altered Fc gamma receptor (Fc ⁇ R) binding affinity or activity include any one or more of amino acid positions 238, 239, 248, 249, 252, 254, 255, 256, 258, 265, 267, 268, 269, 270, 272, 276, 278, 280, 283, 285, 286, 289, 290, 292, 293, 294, 295, 296, 298, 301 , 303, 305, 307, 309, 312, 315, 320, 322, 324, 326, 327, 329, 330, 331 , 333, 334, 335, 337, 338, 340, 360, 373, 376, 378, 382, 388, 389, 398, 414, 416, 419, 430, 434, 435, 437, 438 or 439 of the Fc region.
- Fc ⁇ R Fc gamma receptor
- the parent Fc region used as the template to generate such variants comprises a human IgG Fc region.
- the parent Fc region is preferably not human native sequence lgG3, or the variant Fc region comprising a substitution at position 331 preferably displays increased FcR binding, e.g. to Fc ⁇ RII.
- Variants which display reduced binding to Fc ⁇ RI include those comprising an Fc region amino acid modification at any one or more of amino acid positions 238, 265, 269, 270, 327 or 329.
- Variants which display reduced binding to Fc ⁇ RII include those comprising an Fc region amino acid modification at any one or more of amino acid positions 238, 265, 269, 270, 292, 294, 295, 298, 303, 324, 327, 329, 333, 335, 338, 373, 376, 414, 416, 419, 435, 438 or 439.
- Fc region variants which display reduced binding to Fc ⁇ RIII include those comprising an Fc region amino acid modification at any one or more of amino acid positions 238, 239, 248, 249, 252, 254, 265, 268, 269, 270, 272, 278, 289, 293, 294, 295, 296, 301 , 303, 322, 327, 329, 338, 340, 373, 376, 382, 388, 389, 416, 434, 435 or 437 .
- Fc region variants may comprise an amino acid modification at any one or more of amino acid positions 255, 256, 258, 267, 268, 272, 276, 280, 283, 285, 286, 290, 298, 301 , 305, 307, 309, 312, 315, 320, 322, 326, 330, 331 , 333, 334, 337, 340, 360, 378, 398 or 430 of the Fc region.
- the variant with improved Fc ⁇ R binding activity may display increased binding to Fc ⁇ RIII, and optionally may further display decreased binding to Fc ⁇ RII; e.g. the variant may comprise an amino acid modification at position 298 and/or 333 of an Fc region.
- Variants with increased binding to Fc ⁇ RII include those comprising an amino acid modification at any one or more of amino acid positions 255, 256, 258, 267, 268, 272, 276, 280, 283, 285, 286, 290, 301, 305, 307, 309, 312, 315, 320, 322, 326, 330, 331 , 337, 340, 378, 398 or 430 of an Fc region.
- Such variants may further display decreased binding to Fc ⁇ RIII.
- they may include an Fc region amino acid modification at any one or more of amino acid positions 268, 272, 298, 301 , 322 or 340.
- Fc region variants with altered binding affinity for the neonatal receptor are also contemplated herein.
- Fc region variants with improved affinity for FcRn are anticipated to have longer serum half-lives, and such molecules will have useful applications in methods of treating mammals where long half-life of the administered polypeptide is desired, e.g., to treat a chronic disease or disorder.
- Fc region variants with decreased FcRn binding affinity are expected to have shorter half-lives, and such molecules may, for example, be administered to a mammal where a shortened circulation time may be advantageous, e.g.
- Fc region variants with decreased FcRn binding affinity are anticipated to be less likely to cross the placenta, and thus may be utilized in the treatment of diseases or disorders in pregnant women.
- Fc region variants with altered binding affinity for FcRn include those comprising an Fc region amino acid modification at any one or more of amino acid positions 238, 252, 253, 254, 255, 256, 265, 272, 286, 288, 303, 305, 307, 309, 311 , 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 386, 388, 400, 413, 415, 424, 433, 434, 435, 436, 439 or 447.
- Those which display reduced binding to FcRn will generally comprise an Fc region amino acid modification at any one or more of amino acid positions 252, 253, 254, 255, 288, 309, 386, 388, 400, 415, 433, 435, 436, 439 or 447; and those with increased binding to FcRn will usually comprise an Fc region amino acid modification at any one or more of amino acid positions 238, 256, 265, 272, 286, 303, 305, 307, 311 , 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or 434.
- polypeptide variant(s) prepared as described above may be subjected to further modifications, oftentimes depending on the intended use of the polypeptide. Such modifications may involve further alteration of the amino acid sequence (substitution, insertion and/or deletion of amino acid residues), fusion to heterologous polypeptide(s) and/or covalent modifications. Such "further modifications" may be made prior to, simultaneously with, or following, the amino acid modification(s) disclosed above which result in an alteration of Fc receptor binding and/or ADCC activity. In one embodiment, one may combine the Fc region modification herein with Fc region substitutions disclosed in the references cited in the "Related Art" section of this application. Alternatively or additionally, it may be useful to combine the above amino acid modifications with one or more further amino acid modifications that alter C1q binding and/or complement dependent cytoxicity function of the Fc region.
- the starting polypeptide of particular interest herein is usually one that binds to C1q and displays complement dependent cytotoxicity (CDC).
- CDC complement dependent cytotoxicity
- the further amino acid substitutions described herein will generally serve to alter the ability of the starting polypeptide to bind to C1q and/or modify its complement dependent cytotoxicity function, e.g. to reduce and preferably abolish these effector functions.
- polypeptides comprising substitutions at one or more of the described positions with improved C1q binding and/or complement dependent cytotoxicity (CDC) function are contemplated herein.
- the starting polypeptide may be unable to bind C1q and/or mediate CDC and may be modified according to the teachings herein such that it acquires these further effector functions.
- polypeptides with pre-existing C1q binding activity, optionally further having the ability to mediate CDC may be modified such that one or both of these activities are enhanced.
- the amino acid positions to be modified are generally selected from heavy chain positions 270, 322, 326, 327, 329, 331, 333, and 334, where the numbering of the residues in an IgG heavy chain is that of the EU index as in Kabat etal., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (1991 ). In one embodiment, only one of the eight above-identified positions is altered in order to generate the polypeptide variant region with altered C1q binding and/or WO 00/42072 PCT/TJSOO/00973
- CDC complement dependent cytotoxicity
- substitutions are to be combined, generally substitutions which enhance human C1q binding
- Proline is conserved at position 331 in human IgGI, lgG2 and lgG3, but not lgG4 (which has a serine residue at position 33 ).
- Residue 331 is preferably replaced by alanine or another amino acid, e.g. serine (for IgG regions other than lgG4), glycine or valine.
- Lysine 322 is conserved in human IgGs, and this residue is preferably replaced by an alanine residue, but substitution with any other amino acid residue is contemplated, e.g. serine, threonine, glycine or valine.
- D270 is conserved in human IgGs, and this residue may be replaced by another amino acid residue, e.g. alanine, serine, threonine, glycine, valine, or lysine.
- K326 is also conserved in human IgGs. This residue may be substituted with another residue including, but not limited to, valine, glutamic acid, alanine, glycine, aspartic acid, methionine or tryptophan, with tryptophan being preferred.
- E333 is also conserved in human IgGs.
- E333 is preferably replaced by an amino acid residue with a smaller side chain volume, such as valine, glycine, alanine or serine, with serine being preferred.
- K334 is conserved in human IgGs and may be substituted with another residue such as alanine or other residue.
- residue 327 is an alanine. In order to generate a variant with improved C1q binding, this alanine may be substituted with another residue such as glycine. In lgG2 and lgG4, residue 327 is a glycine and this may be replaced by alanine (or another residue) to diminish C1q binding.
- one can design an Fc region with altered effector function e.g., by modifying C1q binding and/or FcR binding and thereby changing CDC activity and/or ADCC activity.
- one may increase only one of these activities, and optionally also reduce the other activity, e.g. to generate an Fc region variant with improved ADCC activity, but reduced CDC activity and vice versa.
- any cysteine residue not involved in maintaining the proper conformation of the polypeptide variant also may be substituted, generally with serine, to improve the oxidative stability of the molecule and prevent aberrant cross linking.
- Another type of amino acid substitution serves to alter the glycosylation pattern of the polypeptide. This may be achieved by deleting one or more carbohydrate moieties found in the polypeptide, and/or adding one or more glycosylation sites that are not present in the polypeptide.
- Glycosylation of polypeptides is typically either N-linked or O-linked. N-linked refers to the attachment of the carbohydrate moiety to the side chain of an asparagine residue.
- the tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are the recognition sequences for enzymatic attachment of the carbohydrate moiety to the asparagine side chain.
- O-linked glycosylation refers to the attachment of one of the sugars N-aceylgaiactosamine, galactose, or xylose to a hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine may also be used.
- Addition of glycosylation sites to the polypeptide is conveniently accomplished by altering the amino acid sequence such that it contains one or more of the above-described tripeptide sequences (for N-linked glycosylation sites).
- the alteration may also be made by the addition of, or substitution by, one or more serine or threonine residues to the sequence of the original polypeptide (for O-linked glycosylation sites).
- An exemplary glycosylation variant has an amino acid substitution of residue Asn 297 of the heavy chain.
- the class, subclass or allotype of the Fc region may be altered by one or more further amino acid substitutions to generate an Fc region with an amino acid sequence more homologous to a different class, subclass or allotype as desired.
- a murine Fc region may be altered to generate an amino acid sequence more homologous to a human Fc region; a human non-A allotype IgGI Fc region may be modified to achieve a human A allotype IgGI Fc region etc.
- the amino modification(s) herein which alter FcR binding and/or ADCC activity are made in the CH2 domain of the Fc region and the CH3 domain is deleted or WO 00/42072 PCT/TJSOO/00973
- the polypeptide variant may be subjected to one or more assays to evaluate any change in biological activity compared to the starting polypeptide.
- the polypeptide variant essentially retains the ability to bind antigen compared to the nonvariant polypeptide, i.e. the binding capability is no worse than about 20 fold, e.g. no worse than about 5 fold of that of the nonvariant polypeptide.
- the binding capability of the polypeptide variant may be determined using techniques such as fluorescence activated cell sorting (FACS) analysis or radioimmunoprecipitation (RIA), for example.
- the ability of the polypeptide variant to bind an FcR may be evaluated.
- the FcR is a high affinity Fc receptor, such as Fc ⁇ RI, FcRn or Fc ⁇ RIIIA-V158
- binding can be measured by titrating monomeric polypeptide variant and measuring bound polypeptide variant using an antibody which specifically binds to the polypeptide variant in a standard ELISA format (see Example 2 below).
- Another FcR binding assay for low affinity FcRs is described in Examples 1 and 4.
- ADCC activity of the polypeptide variant may be assessed in vivo, e.g., in a animal model such as that disclosed in Clynes et al. PNAS (USA) 95:652-656 (1998).
- the ability of the variant to bind C1q and mediate complement dependent cytotoxicity (CDC) may be assessed.
- a C1q binding ELISA may be performed. Briefly, assay plates may be coated overnight at 4°C with polypeptide variant or starting polypeptide (control) in coating buffer. The plates may then be washed and blocked. Following washing, an aliquot of human C1q may be added to each well and incubated for 2 hrs at room temperature. Following a further wash, 100 ⁇ l of a sheep anti-complement C1q peroxidase conjugated antibody may be added to each well and incubated for 1 hour at room temperature. The plate may again be washed with wash buffer and 100 ⁇ l of substrate buffer containing OPD (O-phenylenediamine dihydrochloride (Sigma)) may be added to each well. The oxidation reaction, observed by the appearance of a yellow color, may be allowed to proceed for 30 minutes and stopped by the addition of 100 ⁇ l of 4.5 N H 2 S0 4 . The absorbance may then read at (492-405) nm.
- OPD O-phenylenediamine dihydr
- An exemplary polypeptide variant is one that displays a "significant reduction in C1q binding" in this assay. This means that about 100 ⁇ g/ml of the polypeptide variant displays about WO 00/42072 PCT/TJSOO/00973
- the polypeptide variant "does not bind C1q", i.e. 100 ⁇ g/ml of the polypeptide variant displays about 100 fold or more reduction in C1q binding compared to 100 ⁇ g/ml of the control antibody.
- Another exemplary variant is one which "has a better binding affinity for human C1q than the parent polypeptide".
- Such a molecule may display, for example, about two-fold or more, and preferably about five-fold or more, improvement in human C1q binding compared to the parent polypeptide (e.g. at the IC 50 values for these two molecules).
- human C1 q binding may be about two-fold to about 500-fold, and preferably from about two-fold or from about five-fold to about 1000-fold improved compared to the parent polypeptide.
- a complement dependent cytotoxicity (CDC) assay may be performed, e.g. as described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996). Briefly, various concentrations of the polypeptide variant and human complement may be diluted with buffer. Cells which express the antigen to which the polypeptide variant binds may be diluted to a density of ⁇ 1 x 10 6 cells /ml. Mixtures of polypeptide variant, diluted human complement and cells expressing the antigen may be added to a flat bottom tissue culture 96 well plate and allowed to incubate for 2 hrs at 37°C and 5% C0 2 to facilitate complement mediated cell lysis.
- CDC complement dependent cytotoxicity
- alamar blue (Accumed International) may then be added to each well and incubated overnight at 37°C.
- the absorbance is measured using a 96-well fluorometer with excitation at 530 nm and emission at 590 nm. The results may be expressed in relative fluorescence units
- the sample concentrations may be computed from a standard curve and the percent activity as compared to nonvariant polypeptide is reported for the polypeptide variant of interest.
- Yet another exemplary variant "does not activate complement".
- 0.6 ⁇ g/ml of the polypeptide variant displays about 0-10% CDC activity in this assay compared to a 0.6 ⁇ g/ml of a control antibody having a nonmutated IgGI Fc region.
- the variant does not appear to have any CDC activity in the above CDC assay.
- the invention also pertains to a polypeptide variant with enhanced CDC compared to a parent polypeptide, e.g., displaying about two-fold to about 100-fold improvement in CDC activity in vitro or in vivo (e.g. at the IC 50 values for each molecule being compared).
- a polypeptide variant with enhanced CDC compared to a parent polypeptide, e.g., displaying about two-fold to about 100-fold improvement in CDC activity in vitro or in vivo (e.g. at the IC 50 values for each molecule being compared).
- a receptor binding assay has been developed herein which is particularly useful for determining binding of an analyte of interest to a receptor where the affinity of the analyte for the receptor is relatively weak, e.g. in the micromolar range as is the case for Fc ⁇ RIIA, Fc ⁇ RIIB, Fc ⁇ RIIIA and Fc ⁇ RIIIB.
- the method involves the formation of a molecular complex that has an improved avidity for the receptor of interest compared to the noncomplexed analyte.
- preferred molecular complex is an immune complex comprising: (a) an Fc region-containing polypeptide (such as an antibody or an immunoadhesin); (b) a first target molecule which comprises at least two binding sites for the Fc region-containing polypeptide; and (c) a second target molecule which comprises at least two binding sites for the first target molecule.
- the Fc region-containing polypeptide is an anti-lgE antibody, such as the E27 antibody (Figs. 4A-4B).
- E27 when mixed with human IgE at an 1 :1 molar ratio, forms a stable hexamer consisting of three E27 molecules and three IgE molecules.
- the "first target molecule” is a chimeric form of IgE in which the Fab portion of an anti- VEGF antibody is fused to the human IgE Fc portion and the "second target molecule” is the antigen to which the Fab binds (i.e. VEGF).
- Each molecule of IgE binds two molecules of VEGF.
- VEGF also binds two molecules of IgE per molecule of VEGF.
- recombinant human VEGF was added at a 2:1 molar ratio to lgE:E27 hexamers, the hexamers were linked into larger molecular weight complexes via the lgE:VEGF interaction (Fig. 5).
- the Fc region of the anti-lgE antibody of the resultant immune complex binds to FcR with higher avidity than either uncomplexed anti-lgE or anti-lgE:lgE hexamers.
- Examples comprising only an Fc region-containing polypeptide:first target molecule combination include an immunoadhesin:ligand combination such as VEGF receptor (KDR)- immunoadhesin:VEGF and a full-length bispecific antibody (bsAb):first target molecule.
- an Fc region-containing polypeptide:f ⁇ rst target molecule:second target molecule combination include a nonblocking antibody.soluble recepto ⁇ ligand combination such as anti-Trk antibody:soluble Trk recepto ⁇ neurotrophin (Urfer et al. J. Biol. Chem. 273(10):5829-5840 (1998)).
- the immune complexes described above have further uses including evaluation of Fc region-containing polypeptide function and immune complex clearance in vivo.
- the immune complex may be administered to a mammal (e.g. in a pre-ciinical animal study) and evaluated for its half-life etc.
- a polypeptide comprising at least the binding domain of the receptor of interest may be coated on solid phase, such as an assay plate.
- the binding domain of the receptor alone or a receptor- fusion protein may be coated on the plate using standard procedures.
- receptor- fusion proteins include receptor-glutathione S-transferase (GST) fusion protein, receptor-chitin binding domain fusion protein, receptor-hexaHis tag fusion protein (coated on glutathione, chitin, and nickel coated plates, respectively).
- GST receptor-glutathione S-transferase
- a capture molecule may be coated on the assay plate and used to bind the receptor-fusion protein via the non-receptor portion of the fusion WO 00/42072 PCT/TJSOO/00973
- binding to cells expressing at least the binding domain of the receptor may be evaluated.
- the cells may be naturally occurring hematopoietic cells that express the FcR of interest or may be transformed with nucleic acid encoding the FcR or a binding domain thereof such that the binding domain is expressed at the surface of the cell to be tested.
- the immune complex described hereinabove is added to the receptor-coated plates and incubated for a sufficient period of time such that the analyte binds to the receptor. Plates may then be washed to remove unbound complexes, and binding of the analyte may be detected according to known methods. For example, binding may be detected using a reagent (e.g. an antibody or fragment thereof) which binds specifically to the analyte, and which is optionally conjugated with a detectable label (detectable labels and methods for conjugating them to polypeptides are described below in the section entitled "Non-Therapeutic Uses for the Polypeptide Variant").
- a reagent e.g. an antibody or fragment thereof
- the reagents can be provided in an assay kit, i.e., a packaged combination of reagents, for combination with the analyte in assaying the ability of the analyte to bind to a receptor of interest.
- the components of the kit will generally be provided in predetermined ratios.
- the kit may provide the first target molecule and/or the second target molecule, optionally complexed together.
- the kit may further include assay plates coated with the receptor or a binding domain thereof (e.g. the extracellular domain of the ⁇ subunit of an FcR).
- kits such as an antibody that binds specifically to the analyte to be assayed, labeled directly or indirectly with an enzymatic label
- the detectable label is an enzyme
- the kit will include substrates and cofactors required by the enzyme (e.g. a substrate precursor which provides the detectable chromophore or fluorophore).
- substrates and cofactors required by the enzyme e.g. a substrate precursor which provides the detectable chromophore or fluorophore
- other additives may be included such as stabilizers, buffers (e.g. assay and/or wash lysis buffer) and the like.
- the relative amounts of the various reagents may be varied widely to provide for concentrations in solution of the reagents that substantially optimize the sensitivity of the assay.
- the reagents may be provided as dry powders, usually lyophilized, including excipients that on dissolution will provide a reagent solution having the appropriate concentration.
- the kit also suitably includes instructions for carrying out the assay.
- the Fc region-containing polypeptide which is modified according to the teachings herein is an antibody.
- Techniques for producing antibodies follow: WO 00/42072 PCT/TJSOO/00973
- the polypeptide is an antibody
- it is directed against an antigen of interest.
- the antigen is a biologically important polypeptide and administration of the antibody to a mammal suffering from a disease or disorder can result in a therapeutic benefit in that mammal.
- antibodies directed against nonpolypeptide antigens are also contemplated.
- the antigen is a polypeptide, it may be a transmembrane molecule (e.g. receptor) or ligand such as a growth factor.
- exemplary antigens include molecules such as renin; a growth hormone, including human growth hormone and bovine growth hormone; growth hormone releasing factor; parathyroid hormone; thyroid stimulating hormone; lipoproteins; alpha-1- antitrypsin; insulin A-chain; insulin B-chain; proinsulin; follicle stimulating hormone; calcitonin; luteinizing hormone; glucagon; clotting factors such as factor VIIIC, factor IX, tissue factor (TF), and von Willebrands factor; anti-clotting factors such as Protein C; atrial natriuretic factor; lung surfactant; a plasminogen activator, such as urokinase or human urine or tissue-type plasminogen activator (t-PA); bombesin; thrombin; hemopoietic growth factor; tumor necrosis factor-alpha and
- CD proteins such as CD3, CD4, CD8, CD19, CD20 and CD34
- members of the ErbB receptor family such as the EGF receptor, HER2, HER3 or HER4 receptor
- cell adhesion molecules such as LFA-1 , Mad , p 50.95, VLA-4, ICAM-1 , VCAM, ⁇ 4/ ⁇ 7 integrin, and ⁇ v/ ⁇ 3 integrin including either ⁇ or ⁇ subunits thereof (e.g.
- anti-CD11a, anti-CD18 or anti-CD11b antibodies growth factors such as VEGF; tissue factor (TF); alpha interferon ( -IFN); an interleukin, such as IL-8; IgE; blood group antigens; flk2/flt3 receptor; obesity (OB) receptor; mpl receptor; CTLA-4; protein C etc.
- growth factors such as VEGF; tissue factor (TF); alpha interferon ( -IFN); an interleukin, such as IL-8; IgE; blood group antigens; flk2/flt3 receptor; obesity (OB) receptor; mpl receptor; CTLA-4; protein C etc.
- Soluble antigens or fragments thereof, optionally conjugated to other molecules, can be used as immunogens for generating antibodies.
- immunogens for transmembrane molecules, such as receptors, fragments of these (e.g. the extracellular domain of a receptor) can be used as the immunogen.
- transmembrane molecules such as receptors
- fragments of these e.g. the extracellular domain of a receptor
- cells expressing the transmembrane molecule can be used as the immunogen.
- Such cells can be derived from a natural source (e.g. cancer cell lines) or may be - cells which have been transformed by recombinant techniques to express the transmembrane molecule.
- Other antigens and forms thereof useful for preparing antibodies will be apparent to those in the art.
- a protein that is immunogenic in the species to be immunized e.g., keyhole limpet hemocyanin, serum albumin, bovine thyrog
- Animals are immunized against the antigen, immunogenic conjugates, or derivatives by combining, e.g., 100 ⁇ g or 5 ⁇ g of the protein or conjugate (for rabbits or mice, respectively) with
- the animals are boosted with 1/5 to 1/10 the original amount of peptide or conjugate in Freund's complete adjuvant by subcutaneous injection at multiple sites. Seven to 14 days later the animals are bled and the serum is assayed for antibody titer. Animals are boosted until the titer plateaus. Preferably, the animal is boosted with the conjugate of the same antigen, but conjugated to a different protein and/or through a different cross-linking reagent. Conjugates also can be made in recombinant cell culture as protein fusions. Also, aggregating agents such as alum are suitably used to enhance the immune response. WO 00/42072 PCT/TJSOO/00973
- Monoclonal antibodies may be made using the hybridoma method first described by Kohler et al., Nature, 256:495 (1975), or may be made by recombinant DNA methods (U.S. Patent No. 4,816,567).
- a mouse or other appropriate host animal such as a hamster or macaque monkey, is immunized as hereinabove described to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the protein used for immunization.
- lymphocytes may be immunized in vitro.
- Lymphocytes then are fused with myeloma cells using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, pp.59-103 (Academic Press, 1986)).
- a suitable fusing agent such as polyethylene glycol
- the hybridoma cells thus prepared are seeded and grown in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells.
- a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells.
- the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (HAT medium), which substances prevent the growth of HGPRT-deficient cells.
- Preferred myeloma cells are those that fuse efficiently, support stable high-level production of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium.
- preferred myeloma cell lines are murine myeloma lines, such as those derived from MOPC-21 and MPC-11 mouse tumors available from the Salk Institute Cell Distribution Center, San Diego, California USA, and SP-2 or X63-Ag8-653 cells available from the American Type Culture Collection, Rockville, Maryland USA.
- Human myeloma and mouse- human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, J. Immunol., 133:3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, pp. 51-63 (Marcel Dekker, Inc., New York, 1987)).
- Culture medium in which hybridoma cells are growing is assayed for production of monoclonal antibodies directed against the antigen.
- the binding specificity of monoclonal antibodies produced by hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA).
- RIA radioimmunoassay
- ELISA enzyme-linked immunoabsorbent assay
- the clones may be subcloned by limiting dilution procedures and grown by standard methods (Goding, Monoclonal Antibodies: Principles and Practice, pp.59-103 (Academic Press, 1986)). Suitable culture media for this purpose include, for example, D-MEM or RPMI-1640 medium.
- the hybridoma cells may be grown in vivo as ascites tumors in an animal.
- the monoclonal antibodies secreted by the subclones are suitably separated from the culture medium, ascites fluid, or serum by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.
- DNA encoding the monoclonal antibodies is readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the monoclonal antibodies).
- the hybridoma cells serve as a preferred source of such DNA.
- the DNA may be placed into expression vectors, which are then transfected into host cells such as E. coli cells, simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. Recombinant production of antibodies will be described in more detail below.
- antibodies or antibody fragments can be isolated from antibody phage libraries generated using the techniques described in McCafferty et al., Nature, 348:552- 554 (1990). Clackson et al., Nature, 352:624-628 (1991) and Marks et al., J. Mol. Biol., 222:581-597 (1991 ) describe the isolation of murine and human antibodies, respectively, using phage libraries.
- the DNA also may be modified, for example, by substituting the coding sequence for human heavy- and light-chain constant domains in place of the homologous murine sequences (U.S. Patent No. 4,816,567; Morrison, etal., Proc. Natl Acad. Sci. USA, 81 :6851 (1984)), or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide.
- non-immunoglobulin polypeptides are substituted for the constant domains of an antibody, or they are substituted for the variable domains of one antigen-combining site of an antibody to create a chimeric bivalent antibody comprising one antigen-combining site having specificity for an antigen and another antigen-combining site having specificity for a different antigen.
- WO 00/42072 PCT/TJSOO/00973
- a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non-human amino acid residues are often referred to as "import" residues, which are typically taken from an "import” variable domain. Humanization can be essentially performed following the method of Winter and co-workers (Jones et al., Nature, 321:522-525 (1986); Riechmann etal., Nature, 332:323-327 (1988); Verhoeyen etal., Science, 239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such "humanized” antibodies are chimeric antibodies (U.S. Patent No.
- humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.
- variable domains both light and heavy
- the choice of human variable domains, both light and heavy, to be used in making the humanized antibodies is very important to reduce antigenicity.
- the sequence of the variable domain of a rodent antibody is screened against the entire library of known human variable-domain sequences.
- the human sequence which is closest to that of the rodent is then accepted as the human framework (FR) for the humanized antibody (Sims et al., J. Immunol., 151:2296 (1993); Chothia et al., J. Mol. Biol., 196:901 (1987)).
- Another method uses a particular framework derived from the consensus sequence of all human antibodies of a particular subgroup of light or heavy chains.
- the same framework may be used for several different humanized antibodies (Carter et al., Proc. Natl. Acad. Sci. USA, 89:4285 (1992); Presta et al., J. Immnol., 151:2623 (1993)).
- humanized antibodies are prepared by a process of analysis of the parental sequences and various conceptual humanized products using three-dimensional models of the parental and humanized sequences.
- Three-dimensional immunoglobulin models are commonly available and are familiar to those skilled in the art.
- Computer programs are available which illustrate and display probable three-dimensional conformational structures of selected candidate immunoglobulin sequences. Inspection of these displays permits analysis of the likely role of the residues in the functioning of the candidate immunoglobulin sequence, i.e., the analysis of residues that influence the ability of the candidate immunoglobulin to bind its antigen.
- FR residues can be selected and combined from the recipient and import sequences so that the desired antibody characteristic, such as increased affinity for the target antigen(s), is achieved.
- WO 00/42072 PCT/TJSOO/00973
- the CDR residues are directly and most substantially involved in influencing antigen binding.
- transgenic animals e.g., mice
- transgenic animals e.g., mice
- J H antibody heavy-chain joining region
- transfer of the human germ-line immunoglobulin gene array in such germ-line mutant mice will result in the production of human antibodies upon antigen challenge. See, e.g., Jakobovits etal., Proc. Natl. Acad. Sci.
- Human antibodies can also be derived from phage-display libraries (Hoogenboom et al., J. Mol. Biol., 227:381 (1991 ); Marks etal., J. Mol. Biol., 222:581-597 (1991); Vaughan etal. Nature Biotech 14:309 (1996)).
- Multispecific antibodies have binding specificities for at least two different antigens. While such molecules normally will only bind two antigens (i.e. bispecific antibodies, BsAbs), antibodies with additional specificities such as trispecific antibodies are encompassed by this expression when used herein.
- BsAbs include those with one arm directed against a tumor cell antigen and the other arm directed against a cytotoxic trigger molecule such as anti-Fc ⁇ RI/anti- CD15, anti-p185 HER2 /Fc ⁇ RIII (CD16), anti-CD3/anti-malignant B-cell (1D10), anti-CD3/anti- p185 HER2 , anti-CD3/anti-p97, anti-CD3/anti-renal cell carcinoma, anti-CD3/anti-OVCAR-3, anti- CD3/L-D1 (anti-colon carcinoma), anti-CD3/anti-melanocyte stimulating hormone analog, anti- EGF receptor/anti-CD3, anti-CD3/anti-CAMA1 , anti-CD3/anti-CD19, anti-CD3/MoV18, anti-neural cell ahesion molecule (NCAM)/anti-CD3, anti-folate binding protein (FBP)/anti-CD3, anti-pan carcinoma associated antigen (AMOC-31 )/anti-CD3; BsAbs with one
- HSV virus
- BsAbs for tumor detection in vitro or in vivo such as anti-CEA/anti-EOTUBE, anti-CEA/anti-DPTA, anti- p185 HE 2 /anti-hapten
- BsAbs as vaccine adjuvants such as anti- rabbit IgG/anti-ferritin, anti-horse radish peroxidase (HRP)/anti-hormone, anti-somatostatin/anti- substance P, anti-HRP/anti-FITC, anti-CEA/anti- ⁇ -gaiactosidase.
- HRP anti-horse radish peroxidase
- HRP anti-somatostatin/anti- substance P
- anti-HRP/anti-FITC anti-CEA/anti- ⁇ -gaiactosidase.
- trispecific antibodies examples include anti-CD3/anti-CD4/anti-CD37, anti-CD3/anti-CD5/anti-CD37 and anti-CD3/anti- CD8/anti-CD37.
- Bispecific antibodies can be prepared as full length antibodies or antibody fragments (e.g. F(ab') 2 bispecific antibodies).
- bispecific antibodies are known in the art. Traditional production of full length bispecific antibodies is based on the coexpression of two immunoglobulin heavy chain- light chain pairs, where the two chains have different specificities (Millstein et al., Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of 10 different antibody molecules, of which only one has the correct bispecific structure. Purification of the correct molecule, which is usually done by affinity chromatography steps, is rather cumbersome, and the product yields are low. Similar procedures are disclosed in WO 93/08829, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).
- antibody variable domains with the desired binding specificities are fused to immunoglobulin constant domain sequences.
- the fusion preferably is with an immunoglobulin heavy chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. It is preferred to have the first heavy-chain constant region (CH1 ) containing the site necessary for light chain binding, present in at least one of the fusions.
- DNAs encoding the immunoglobulin heavy chain fusions and, if desired, the immunoglobulin light chain are inserted into separate expression vectors, and are co-transfected into a suitable host organism.
- the bispecific antibodies are composed of a hybrid immunoglobulin heavy chain with a first binding specificity in one arm, and a hybrid immunoglobulin heavy chain-light chain pair (providing a second binding specificity) in the other arm. It was found that this asymmetric structure facilitates the separation of the desired bispecific compound from unwanted immunoglobulin chain combinations, as the presence of an WO 00/42072 PCT/TJSOO/00973
- the interface between a pair of antibody molecules can be engineered to maximize the percentage of heterodimers which are recovered from recombinant cell culture.
- the preferred interface comprises at least a part of the C H 3 domain of an antibody constant domain.
- one or more small amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g. tyrosine or tryptophan).
- Compensatory "cavities" of identical or similar size to the large side chain(s) are created on the interface of the second antibody molecule by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). This provides a mechanism for increasing the yield of the heterodimer over other unwanted end-products such as homodimers.
- Bispecific antibodies include cross-linked or "heteroconjugate" antibodies.
- one of the antibodies in the heteroconjugate can be coupled to avidin, the other to biotin.
- Such antibodies have, for example, been proposed to target immune system cells to unwanted cells (US Patent No. 4,676,980), and for treatment of HIV infection (WO 91/00360, WO 92/200373, and EP 03089).
- Heteroconjugate antibodies may be made using any convenient cross-linking methods. Suitable cross-linking agents are well known in the art, and are disclosed in US Patent No. 4,676,980, along with a number of cross-linking techniques.
- Antibodies with more than two valencies are contemplated.
- trispecific antibodies can be prepared. Tutt et al. J. Immunol. 147: 60 (1991 ).
- polypeptide of interest herein is preferably an antibody
- Fc region- containing polypeptides which can be modified according to the methods described herein are contemplated.
- An example of such a molecule is an immunoadhesin.
- the simplest and most straightforward immunoadhesin design combines the binding domain(s) of the adhesin (e.g. the extracellular domain (ECD) of a receptor) with the Fc region of an immunoglobulin heavy chain.
- ECD extracellular domain
- nucleic acid encoding the binding domain of the adhesin will be fused C- terminally to nucleic acid encoding the N-terminus of an immunoglobulin constant domain sequence, however N-terminal fusions are also possible.
- the encoded chimeric polypeptide will retain at least functionally active hinge, C H 2 and C H 3 domains of the constant region of an immunoglobulin heavy chain. Fusions are also made to the C-terminus of the Fc portion of a constant domain, or immediately N-terminal to the C H 1 of the heavy chain or the corresponding region of the light chain.
- the precise site at which the fusion is made is not critical; particular sites are well known and may be selected in order to optimize the biological activity, secretion, or binding characteristics of the immunoadhesin.
- the adhesin sequence is fused to the N-terminus of the Fc region of immunoglobulin G ⁇ (IgG,)- It is possible to fuse the entire heavy chain constant region to the adhesin sequence. However, more preferably, a sequence beginning in the hinge region just upstream of the papain cleavage site which defines IgG Fc chemically (i.e. residue 216, taking the first residue of heavy chain constant region to be 114), or analogous sites of other immunoglobulins is used in the fusion.
- the adhesin amino acid sequence is fused to (a) the hinge region and C H 2 and C H 3 or (b) the C H 1 , hinge, C H 2 and C H 3 domains, of an IgG heavy chain.
- the immunoadhesins are assembled as multimers, and particularly as heterodimers or heterotetramers.
- these assembled immunoglobulins will have known unit structures.
- a basic four chain structural unit is the form in which IgG, IgD, and IgE exist.
- a four chain unit is repeated in the higher molecular weight immunoglobulins; IgM generally exists as a pentamer of four basic units held together by disulfide bonds.
- IgA globulin, and occasionally IgG globulin may also exist in multimeric form in serum. In the case of multimer, each of the four units may be the same or different.
- V L is an immunoglobulin light chain variable domain
- V H is an immunoglobulin heavy chain variable domain
- C L is an immunoglobulin light chain constant domain
- C H is an immunoglobulin heavy chain constant domain
- n is an integer greater than 1 ;
- Y designates the residue of a covalent cross-linking agent.
- the adhesin sequences can be inserted between immunoglobulin heavy chain and light chain sequences, such that an immunoglobulin comprising a chimeric heavy chain is obtained.
- the adhesin sequences are fused to the 3' end of an immunoglobulin heavy chain in each arm of an immunoglobulin, either between the hinge and the C H 2 domain, or between the C H 2 and C H 3 domains. Similar constructs have been reported by Hoogenboom, etal., Mol. Immunol. 28:1027-1037 (1991 ).
- an immunoglobulin light chain might be present either covalently associated to an adhesin-immunoglobulin heavy chain fusion polypeptide, or directly fused to the adhesin.
- DNA encoding an immunoglobulin light chain is typically coexpressed with the DNA encoding the adhesin-immunoglobulin heavy chain fusion protein.
- the hybrid heavy chain and the light chain will be covalently associated to provide an immunoglobulin-like structure comprising two disulfide-linked immunoglobulin heavy chain-light chain pairs.
- Immunoadhesins are most conveniently constructed by fusing the cDNA sequence encoding the adhesin portion in-frame to an immunoglobulin cDNA sequence.
- fusion to genomic immunoglobulin fragments can also be used (see, e.g. Aruffo et al., Cell 61 :1303- 1313 (1990); and Stamenkovic et al., Cell 66:1133-1144 (1991)).
- the latter type of fusion requires the presence of Ig regulatory sequences for expression.
- cDNAs encoding IgG heavy- chain constant regions can be isolated based on published sequences from cDNA libraries derived from spleen or peripheral blood lymphocytes, by hybridization or by polymerase chain reaction (PCR) techniques.
- the cDNAs encoding the "adhesin" and the immunoglobulin parts of the immunoadhesin are inserted in tandem into a plasmid vector that directs efficient expression in the chosen host cells.
- the invention also provides isolated nucleic acid encoding a polypeptide variant as disclosed herein, vectors and host cells comprising the nucleic acid, and recombinant techniques for the production of the polypeptide variant.
- the nucleic acid encoding it is isolated and inserted into a replicable vector for further cloning (amplification of the DNA) or for expression.
- DNA encoding the polypeptide variant is readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the polypeptide variant).
- Many vectors are available.
- the vector components generally include, but are not limited to, one or more of the following: a signal sequence, an origin of replication, one or more marker genes, an enhancer element, a promoter, and a transcription termination sequence.
- polypeptide variant of this invention may be produced recombinantly not only directly, but also as a fusion polypeptide with a heterologous polypeptide, which is preferably a signal sequence or other polypeptide having a specific cleavage site at the N-terminus of the mature protein or polypeptide.
- a heterologous polypeptide which is preferably a signal sequence or other polypeptide having a specific cleavage site at the N-terminus of the mature protein or polypeptide.
- the heterologous signal sequence selected preferably is one that is recognized and processed (i.e., cleaved by a signal peptidase) by the host cell.
- the signal sequence is substituted by a prokaryotic signal sequence selected, for example, from the group of the alkaline phosphatase, penicillinase, Ipp, or heat-stable enterotoxin II leaders.
- a prokaryotic signal sequence selected, for example, from the group of the alkaline phosphatase, penicillinase, Ipp, or heat-stable enterotoxin II leaders.
- yeast secretion the native signal sequence may be substituted by, e.g., the yeast invertase leader, ⁇ factor leader (including Saccharomyces and Kluyveromyces ⁇ -factor leaders), or acid phosphatase leader, the C. albicans glucoamylase leader, or the signal described in WO 90/13646.
- mammalian signal sequences as well as viral secretory leaders for example, the herpes simplex gD signal, are available.
- the DNA for such precursor region is ligated in reading frame to DNA encoding the polypeptide variant.
- Both expression and cloning vectors contain a nucleic acid sequence that enables the vector to replicate in one or more selected host cells. Generally, in cloning vectors this sequence is one that enables the vector to replicate independently of the host chromosomal DNA, and includes origins of replication or autonomously replicating sequences. Such sequences are well known for a variety of bacteria, yeast, and viruses.
- the origin of replication from the plasmid pBR322 is suitable for most Gram-negative bacteria, the 2 ⁇ plasmid origin is suitable for yeast, and various viral origins (SV40, polyoma, adenovirus, VSV or BPV) are useful for cloning vectors in mammalian cells. Generally, the origin of replication component is not needed for mammalian expression vectors (the SV40 origin may typically be used only because it contains the early promoter).
- Selection gene component Expression and cloning vectors may contain a selection gene, also termed a selectable marker. Typical selection genes encode proteins that (a) confer resistance to antibiotics or other toxins, e.g., ampicillin, neomycin, methotrexate, or tetracycline, (b) complement auxotrophic WO 00/42072 PCT/TJSOO/00973
- One example of a selection scheme utilizes a drug to arrest growth of a host cell. Those cells that are successfully transformed with a heterologous gene produce a protein conferring drug resistance and thus survive the selection regimen. Examples of such dominant selection use the drugs neomycin, mycophenolic acid and hygromycin.
- suitable selectable markers for mammalian cells are those that enable the identification of cells competent to take up the polypeptide variant nucleic acid, such as DHFR, thymidine kinase, metallothionein-l and -II, preferably primate metallothionein genes, adenosine deaminase, ornithine decarboxylase, etc.
- cells transformed with the DHFR selection gene are first identified by culturing all of the transformants in a culture medium that contains methotrexate (Mtx), a competitive antagonist of DHFR.
- Mtx methotrexate
- An appropriate host cell when wild-type DHFR is employed is the Chinese hamster ovary (CHO) cell line deficient in DHFR activity.
- host cells transformed or co-transformed with DNA sequences encoding polypeptide variant, wild-type DHFR protein, and another selectable marker such as aminoglycoside 3'-phosphotransferase (APH) can be selected by cell growth in medium containing a selection agent for the selectable marker such as an aminoglycosidic antibiotic, e.g., kanamycin, neomycin, or G418. See U.S. Patent No. 4,965,199.
- APH aminoglycoside 3'-phosphotransferase
- a suitable selection gene for use in yeast is the _rp1 gene present in the yeast plasmid YRp7 (Stinchcomb etal., Nature, 282:39 (1979)).
- the trp ⁇ gene provides a selection marker for a mutant strain of yeast lacking the ability to grow in tryptophan, for example, ATCC No. 44076 or PEP4-1. Jones, Genetics, 85:12 (1977).
- the presence of the trp lesion in the yeast host cell genome then provides an effective environment for detecting transformation by growth in the absence of tryptophan.
- Le ⁇ /2-deficient yeast strains (ATCC 20,622 or 38,626) are complemented by known plasmids bearing the Leu2 gene.
- vectors derived from the 1.6 ⁇ m circular plasmid pKD1 can be used for transformation of Kluyveromyces yeasts.
- an expression system for large-scale production of recombinant calf chymosin was reported for K. lactis. Van den Berg, Bio/Technology, 8:135 (1990).
- Stable multi-copy expression vectors for secretion of mature recombinant human serum albumin by industrial strains of Kluyveromyces have also been disclosed. Fleer et al., Bio/Technology, 9:968-975 (1991 ).
- Expression and cloning vectors usually contain a promoter that is recognized by the host organism and is operably linked to the polypeptide variant nucleic acid.
- Promoters suitable for use with prokaryotic hosts include the phoA promoter, ⁇ -lactamase and lactose promoter systems, alkaline phosphatase, a tryptophan (trp) promoter system, and hybrid promoters such as the tac promoter.
- trp tryptophan
- Other known bacterial promoters are suitable. Promoters for use in bacterial systems also will contain a Shine-Dalgarno (S.D.) sequence operably linked to the DNA encoding the polypeptide variant.
- S.D. Shine-Dalgarno
- Promoter sequences are known for eukaryotes. Virtually all eukaryotic genes have an AT- rich region located approximately 25 to 30 bases upstream from the site where transcription is initiated. Another sequence found 70 to 80 bases upstream from the start of transcription of many genes is a CNCAAT region where N may be any nucleotide. At the 3' end of most eukaryotic genes is an AATAAA sequence that may be the signal for addition of the poly A tail to the 3' end of the coding sequence. All of these sequences are suitably inserted into eukaryotic expression vectors.
- suitable promoting sequences for use with yeast hosts include the promoters for 3-phosphoglycerate kinase or other glycolytic enzymes, such as enolase, glyceraldehyde-3- phosphate dehydrogenase, hexokinase, pyruvate decarboxylase, phosphofructokinase, glucose-
- 6-phosphate isomerase 3-phosphoglycerate mutase, pyruvate kinase, triosephosphate isomerase, phosphoglucose isomerase, and glucokinase.
- yeast promoters which are inducible promoters having the additional advantage of transcription controlled by growth conditions, are the promoter regions for alcohol dehydrogenase 2, isocytochrome C, acid phosphatase, degradative enzymes associated with nitrogen metabolism, metallothionein, glyceraldehyde-3-phosphate dehydrogenase, and enzymes responsible for maltose and galactose utilization.
- Suitable vectors and promoters for use in yeast expression are further described in EP 73,657.
- Yeast enhancers also are advantageously used with yeast promoters.
- Polypeptide variant transcription from vectors in mammalian host cells is controlled, for example, by promoters obtained from the genomes of viruses such as polyoma virus, fowlpox virus, adenovirus (such as Adenovirus 2), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-B virus and most preferably Simian Virus 40 (SV40), from heterologous mammalian promoters, e.g., the actin promoter or an immunoglobulin promoter, from heat-shock promoters, provided such promoters are compatible with the host cell systems.
- viruses such as polyoma virus, fowlpox virus, adenovirus (such as Adenovirus 2), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-B virus and most preferably Simian Virus 40 (
- the early and late promoters of the SV40 virus are conveniently obtained as an SV40 restriction fragment that also contains the SV40 viral origin of replication.
- promoter of the human cytomegalovirus is conveniently obtained as a Hindlll E restriction fragment.
- a system for expressing DNA in mammalian hosts using the bovine papiiloma virus as a vector is disclosed in U.S. Patent No. 4,419,446. A modification of this system is described in U.S. Patent No. 4,601,978. See also Reyes et al., Nature 297:598-601 (1982) on expression of human ⁇ -interferon cDNA in mouse cells under the control of a thymidine kinase promoter from herpes simplex virus. Alternatively, the rous sarcoma virus long terminal repeat can be used as the promoter.
- Enhancer element component Transcription of a DNA encoding the polypeptide variant of this invention by higher eukaryotes is often increased by inserting an enhancer sequence into the vector.
- enhancer sequences are now known from mammalian genes (globin, elastase, albumin, ⁇ -fetoprotein, and insulin). Typically, however, one will use an enhancer from a eukaryotic cell virus. Examples include the SV40 enhancer on the late side of the replication origin (bp 100-270), the cytomegalovirus early promoter enhancer, the polyoma enhancer on the late side of the replication origin, and adenovirus enhancers.
- the enhancer may be spliced into the vector at a position 5' or 3' to the polypeptide variant-encoding sequence, but is preferably located at a site 5' from the promoter.
- Transcription termination component Expression vectors used in eukaryotic host cells (yeast, fungi, insect, plant, animal, human, or nucleated cells from other multicellular organisms) will also contain sequences necessary for the termination of transcription and for stabilizing the mRNA. Such sequences are commonly available from the 5' and, occasionally 3', untranslated regions of eukaryotic or viral DNAs or cDNAs. These regions contain nucleotide segments transcribed as polyadenylated fragments in the untranslated portion of the mRNA encoding the polypeptide variant.
- One useful transcription termination component is the bovine growth hormone polyadenylation region. See W094/11026 and the expression vector disclosed therein.
- Suitable host cells for cloning or expressing the DNA in the vectors herein are the prokaryote, yeast, or higher eukaryote cells described above.
- Suitable prokaryotes for this purpose include eubacteria, such as Gram-negative or Gram-positive organisms, for example, Enterobacteriaceae such as Escherichia, e.g., E. coli, Enterobacter, Erwinia, Klebsiella, Proteus, Salmonella, e.g., Salmonella typhimurium, Serratia, e.g., Serratia marcescans, and Shigella, as well as Bacilli such as B. subtilis and ⁇ .
- Enterobacteriaceae such as Escherichia, e.g., E. coli, Enterobacter, Erwinia, Klebsiella, Proteus
- Salmonella e.g., Salmonella typhimurium
- Serratia e.g.
- licheniformis e.g., B. licheniformis 41 P disclosed in DD 266,710 published 12 April 1989
- Pseudomonas such as P. aeruginosa
- E. coli 294 ATCC 31 ,446
- other strains such as E. co// B, £. co//X1776 (ATCC 31 ,537), and E. coli W3110 (ATCC 27,325) are suitable.
- E. coli 294 ATCC 31 ,446
- other strains such as E. co// B, £. co//X1776 (ATCC 31 ,537)
- E. coli W3110 ATCC 27,325
- eukaryotic microbes such as filamentous fungi or yeast are suitable cloning or expression hosts for polypeptide variant-encoding vectors.
- Saccharomyces cerevisiae or common baker's yeast, is the most commonly used among lower eukaryotic host microorganisms.
- a number of other genera, species, and strains are commonly available and useful herein, such as Schizosaccharomyces pombe; Kluyveromyces hosts such as, e.g., K. lactis, K. fragilis (ATCC 12,424), K. bulgaricus (ATCC 16,045), K. wickeramii (ATCC 24,178), K.
- waltii ATCC 56,500
- K. drosophilarum ATCC 36,906
- K . thermotolerans K. marxianus
- yarrowia EP 402,226
- Pichia pastoris EP 183,070
- Candida Trichoderma reesia
- Neurospora crassa Schwanniomyces such as Schwanniomyces occidentalis
- filamentous fungi such as, e.g., Neurospora, Penicillium, Tolypocladium, and Aspergillus hosts such as A. nidulans and A. niger.
- Suitable host cells for the expression of glycosylated polypeptide variant are derived from multicellular organisms.
- invertebrate cells include plant and insect cells.
- Numerous baculoviral strains and variants and corresponding permissive insect host cells from hosts such as Spodoptera frugiperda (caterpillar), Aedes aegypti (mosquito), Aedes albopictus (mosquito), Drosophila melanogaster (fruitfly), and Bombyx mori have been identified.
- a variety of viral strains for transfection are publicly available, e.g., the L-1 variant of Autographa califomica NPV and the Bm-5 strain of Bombyx mori NPV, and such viruses may be used as the virus herein according to the present invention, particularly for transfection of Spodoptera frugiperda cells.
- Plant cell cultures of cotton, com, potato, soybean, petunia, tomato, and tobacco can also be utilized as hosts.
- vertebrate cells have been greatest in vertebrate cells, and propagation of vertebrate cells in culture (tissue culture) has become a routine procedure.
- useful mammalian host cell lines are monkey kidney CV1 line transformed by SV40 (COS-7, ATCC CRL 1651 ); human embryonic kidney line (293 or 293 cells subcloned for growth in suspension culture, Graham et al., J. Gen Virol. 36:59 (1977)); baby hamster kidney cells (BHK, ATCC CCL 10); Chinese hamster ovary cells/-DHFR (CHO, Urlaub et al., Proc. Natl. Acad. Sci. USA 77:4216 (1980)); mouse sertoli cells (TM4, Mather, Biol. Reprod.
- SV40 monkey kidney CV1 line transformed by SV40
- human embryonic kidney line (293 or 293 cells subcloned for growth in suspension culture, Graham et al., J. Gen Virol. 36:59 (1977)
- baby hamster kidney cells
- monkey kidney cells (CV1 ATCC CCL 70); African green monkey kidney cells (VERO-76, ATCC CRL-1587); human cervical carcinoma cells (HELA, ATCC CCL 2); canine kidney cells (MDCK, ATCC CCL 34); buffalo rat liver cells (BRL 3A, ATCC CRL 1442); human lung cells (W138, ATCC CCL 75); human WO 00/42072 PCT/TJSOO/00973
- Hep G2 liver cells
- MMT 060562 mouse mammary tumor
- TRI cells Meather etal., Annals N.Y. Acad. Sci. 383:44-68 (1982)
- MRC 5 cells FS4 cells
- a human hepatoma line Hep G2
- Host cells are transformed with the above-described expression or cloning vectors for polypeptide variant production and cultured in conventional nutrient media modified as appropriate for inducing promoters, selecting transformants, or amplifying the genes encoding the desired sequences.
- the host cells used to produce the polypeptide variant of this invention may be cultured in a variety of media.
- Commercially available media such as Ham's F10 (Sigma), Minimal Essential Medium ((MEM), (Sigma), RPMI-1640 (Sigma), and Dulbecco's Modified Eagle's Medium ((DMEM), Sigma) are suitable for culturing the host cells.
- any of these media may be supplemented as necessary with hormones and/or other growth factors (such as insulin, transfe ⁇ in, or epidermal growth factor), salts (such as sodium chloride, calcium, magnesium, and phosphate), buffers (such as HEPES), nucleotides (such as adenosine and thymidine), antibiotics (such as GENTAMYCINTM drug), trace elements (defined as inorganic compounds usually present at final concentrations in the micromolar range), and glucose or an equivalent energy source. Any other necessary supplements may also be included at appropriate concentrations that would be known to those skilled in the art.
- the culture conditions such as temperature, pH, and the like, are those previously used with the host cell selected for expression, and will be apparent to the ordinarily skilled artisan.
- the polypeptide variant can be produced intracellularly, in the periplasmic space, or directly secreted into the medium. If the polypeptide variant is produced intracellularly, as a first step, the particulate debris, either host cells or lysed fragments, is removed, for example, by centrifugation or ultrafiltration. Carter et al., Bio/Technology 10:163-167 (1992) describe a procedure for isolating antibodies which are secreted to the periplasmic space of E. coli. Briefly, cell paste is thawed in the presence of sodium acetate (pH 3.5), EDTA, and phenylmethylsulfonylfluoride (PMSF) over about 30 min.
- sodium acetate pH 3.5
- EDTA EDTA
- PMSF phenylmethylsulfonylfluoride
- a protease inhibitor such as PMSF may be included in any of the foregoing steps to inhibit proteolysis and antibiotics may be included to prevent the growth of adventitious contaminants.
- the polypeptide variant composition prepared from the cells can be purified using, for example, hydroxylapatite chromatography, gel electrophoresis, dialysis, and affinity chromatography, with affinity chromatography being the preferred purification technique.
- affinity chromatography is the preferred purification technique.
- the suitability of protein A as an affinity ligand depends on the species and isotype of any immunoglobulin Fc region that is present in the polypeptide variant.
- Protein A can be used to purify polypeptide variants that are based on human ⁇ 1 , ⁇ 2, or ⁇ 4 heavy chains (Lindmark et al., J. Immunol. Meth. 62:1-13 (1983)). Protein G is recommended for all mouse isotypes and for human ⁇ 3 (Guss et al., EMBO J.
- the matrix to which the affinity ligand is attached is most often agarose, but other matrices are available.
- Mechanically stable matrices such as controlled pore glass or poly(styrenedivinyl)benzene allow for faster flow rates and shorter processing times than can be achieved with agarose.
- the Bakerbond ABXTM resin J. T. Baker, Phillipsburg, NJ is useful for purification.
- the mixture comprising the polypeptide variant of interest and contaminants may be subjected to low pH hydrophobic interaction chromatography using an elution buffer at a pH between about 2.5-4.5, preferably performed at low salt concentrations (e.g.,from about 0-0.25M salt).
- low salt concentrations e.g.,from about 0-0.25M salt.
- Therapeutic formulations of the polypeptide variant are prepared for storage by mixing the polypeptide variant having the desired degree of purity with optional physiologically acceptable carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences 16th edition, Osol, A.
- Acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) WO 00/42072 PCT/TJSOO/00973
- polypeptide polypeptide
- proteins such as serum albumin, gelatin, or immunoglobulins
- hydrophilic polymers such as polyvinylpyrrolidone
- amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine
- chelating agents such as EDTA
- sugars such as sucrose, mannitol, trehalose or sorbitol
- salt-forming counter-ions such as sodium
- metal complexes e.g., Zn-protein complexes
- non-ionic surfactants such as TWEENTM, PLURONICSTM or polyethylene glycol (PEG).
- the formulation herein may also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other.
- Such molecules are suitably present in combination in amounts that are effective for the purpose intended.
- the active ingredients may also be entrapped in microcapsule prepared, for example, by coacervation techniques or by interfaciai polymerization, for example, hydroxymethylcellulose or gelatin-microcapsule and poly-(methylmethacylate) microcapsule, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles and nanocapsules) or in macroemulsions.
- colloidal drug delivery systems for example, liposomes, albumin microspheres, microemulsions, nano-particles and nanocapsules
- sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the polypeptide variant, which matrices are in the form of shaped articles, e.g., films, or microcapsule.
- sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No.
- copolymers of L-glutamic acid and ⁇ ethyl-L-glutamate copolymers of L-glutamic acid and ⁇ ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOTTM (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(-)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods.
- encapsulated antibodies When encapsulated antibodies remain in the body for a long time, they may denature or aggregate as a result of exposure to moisture at 37°C, resulting in a loss of biological activity and possible changes in immunogenicity. Rational strategies can be devised for stabilization depending on the mechanism involved. For example, if the aggregation mechanism is discovered to be intermolecular S-S bond formation through thio-disulfide interchange, stabilization may be achieved by modifying sulfhydryl residues, lyophilizing from acidic solutions, controlling moisture content, using appropriate additives, and developing specific polymer matrix compositions.
- the polypeptide variant of the invention may be used as an affinity purification agent.
- the polypeptide variant is immobilized on a solid phase such a Sephadex resin or filter paper, using methods well known in the art.
- the immobilized polypeptide variant is contacted with a sample containing the antigen to be purified, and thereafter the support is washed with a suitable solvent that will remove substantially all the material in the sample except the antigen to be purified, which is bound to the immobilized polypeptide variant. Finally, the support is washed with another suitable solvent, such as glycine buffer, pH 5.0, that will release the antigen from the polypeptide variant.
- the polypeptide variant may also be useful in diagnostic assays, e.g., for detecting expression of an antigen of interest in specific cells, tissues, or serum.
- polypeptide variant typically will be labeled with a detectable moiety.
- labels are available which can be generally grouped into the following categories:
- Radioisotopes such as 35 S, 14 C, 125 l, 3 H, and 131 l.
- the polypeptide variant can be labeled with the radioisotope using the techniques described in Current Protocols in Immunology, Volumes 1 and 2, Coligen et al., Ed. Wiley-lnterscience, New York, New York, Pubs. (1991 ) for example and radioactivity can be measured using scintillation counting.
- Fluorescent labels such as rare earth chelates (europium chelates) or fluorescein and its derivatives, rhodamine and its derivatives, dansyl, Lissamine, phycoerythrin and Texas Red are available.
- the fluorescent labels can be conjugated to the polypeptide variant using the techniques disclosed in Current Protocols in Immunology, supra, for example. Fluorescence can be quantified using a fluorimeter.
- the enzyme generally catalyzes a chemical alteration of the chromogenic substrate that can be measured using various techniques. For example, the enzyme may catalyze a color change in a substrate, which can be measured spectrophotometrically. Alternatively, the enzyme may alter the fluorescence or chemiluminescence of the substrate. Techniques for quantifying a change in fluorescence are described above.
- the chemiluminescent substrate becomes electronically excited by a chemical reaction and may then emit light which can be measured (using a chemiluminometer, for example) or donates energy to a fluorescent acceptor.
- enzymatic labels include luciferases (e.g., firefly luciferase and bacterial luciferase; U.S. Patent No. 4,737,456), luciferin, 2,3-dihydrophthalazinediones, malate dehydrogenase, urease, peroxidase such as horseradish peroxidase (HRPO), alkaline phosphatase, ⁇ -galactosidase, glucoamyiase, lysozyme, saccharide oxidases (e.g., glucose oxidase, galactose oxidase, and glucose-6-phosphate dehydrogenase), heterocyclic oxidases
- luciferases e.g., firefly luciferase and bacterial luciferase; U.S. Patent No. 4,737,456
- peroxidase such as horseradish peroxidase (HRPO
- enzyme-substrate combinations include, for example:
- HRPO Horseradish peroxidase
- OPD anthophenylene diamine
- TMB 3,3',5,5'-tetramethyl benzidine hydrochloride
- ⁇ -D-galactosidase ( ⁇ -D-Gal) with a chromogenic substrate (e.g., p-nitrophenyl- ⁇ - D-galactosidase) or fluorogenic substrate 4-methylumbelliferyl- ⁇ -D-galactosidase.
- a chromogenic substrate e.g., p-nitrophenyl- ⁇ - D-galactosidase
- fluorogenic substrate 4-methylumbelliferyl- ⁇ -D-galactosidase
- the label is indirectly conjugated with the polypeptide variant.
- the polypeptide variant can be conjugated with biotin and any of the three broad categories of labels mentioned above can be conjugated with avidin, or Wee versa. Biotin binds selectively to avidin and thus, the label can be conjugated with the polypeptide variant in this indirect manner.
- the polypeptide variant is conjugated with a small hapten (e.g., digoxin) and one of the different types of labels mentioned above is conjugated with an anti-hapten polypeptide variant (e.g., anti-digoxin antibody).
- an anti-hapten polypeptide variant e.g., anti-digoxin antibody
- the polypeptide variant need not be labeled, and the presence thereof can be detected using a labeled antibody which binds to the polypeptide variant.
- the polypeptide variant of the present invention may be employed in any known assay method, such as competitive binding assays, direct and indirect sandwich assays, and immunoprecipitation assays. Zola, Monoclonal Antibodies: A Manual of Techniques, pp.147- 158 (CRC Press, Inc. 1987).
- the polypeptide variant may also be used for in vivo diagnostic assays.
- the polypeptide variant is labeled with a radionuclide (such as 111 ln, "Tc, 14 C, 131 l, 125 l, 3 H, 32 P or 35 S) so that the antigen or cells expressing it can be localized using immunoscintiography.
- a radionuclide such as 111 ln, "Tc, 14 C, 131 l, 125 l, 3 H, 32 P or 35 S
- the polypeptide variant of the present invention may be used to treat a mammal e.g. a patient suffering from, or predisposed to, a disease or disorder who could benefit from administration of the polypeptide variant.
- the conditions which can be treated with the polypeptide variant are many and include cancer (e.g.
- polypeptide variant binds the HER2 receptor, CD20 or vascular endothelial growth factor (VEGF)); allergic conditions such as asthma (with an anti-lgE antibody); and LFA-1 -mediated disorders (e.g. where the polypeptide variant is an anti-LFA-1 or anti-ICAM-1 antibody) etc.
- VEGF vascular endothelial growth factor
- the disorder preferably is HER2-expressing cancer, e.g. a benign or malignant tumor characterized by overexpression of the HER2 receptor.
- cancers include, but are not limited to, breast cancer, squamous cell cancer, small-cell lung cancer, non-small cell lung cancer, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, bladder cancer, hepatoma, colon cancer, colorectal cancer, endometrial carcinoma, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma and various types of head and neck cancer.
- a polypeptide with a variant Fc region which has improved, or diminished, ADCC activity. Such molecules will find applications in the treatment of different disorders.
- the polypeptide variant with improved ADCC activity may be employed in the treatment of diseases or disorders where destruction or elimination of tissue or foreign microorganisms is desired.
- the polypeptide may be used to treat cancer; inflammatory disorders; infections (e.g. bacterial, viral, fungal or yeast infections); and other conditions (such as goiter) where removal of tissue is desired, etc.
- the polypeptide variant may be used to treat diseases or disorders where a Fc region-containing polypeptide with long half-life is desired, but the polypeptide preferably does not have undesirable effector function(s).
- the Fc region-containing polypeptide may be an anti-tissue factor (TF) antibody; anti-lgE antibody; and anti-integrin antibody (e.g. an anti- ⁇ 4 ⁇ 7 antibody).
- TF tissue factor
- anti-lgE antibody anti-integrin antibody
- the desired mechanism of action of such Fc region-containing polypeptides may be to block ligand-receptor binding pairs.
- the Fc-region containing polypeptide with diminished ADCC activity may be an agonist antibody.
- the polypeptide variant is administered by any suitable means, including parenteral, subcutaneous, intraperitoneal, intrapulmonary, and intranasal, and, if desired for local immunosuppressive treatment, intralesional administration.
- Parenteral infusions include intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration.
- the polypeptide variant is suitably administered by pulse infusion, particularly with declining doses of the polypeptide variant.
- the dosing is given by injections, most preferably intravenous or subcutaneous injections, depending in part on whether the administration is brief or chronic.
- polypeptide variant For the prevention or treatment of disease, the appropriate dosage of polypeptide variant will depend on the type of disease to be treated, the severity and course of the disease, whether the polypeptide variant is administered for preventive or therapeutic purposes, previous therapy, the patient's clinical history and response to the polypeptide variant, and the discretion of the attending physician.
- the polypeptide variant is suitably administered to the patient at one time or over a series of treatments. Depending on the type and severity of the disease, about 1 ⁇ g/kg to 15 mg/kg (e.g., 0.1-
- 20mg/kg of polypeptide variant is an initial candidate dosage for administration to the patient, whether, for example, by one or more separate administrations, or by continuous infusion.
- a typical daily dosage might range from about 1 ⁇ g/kg to 100 mg/kg or more, depending on the factors mentioned above.
- the treatment is sustained until a desired suppression of disease symptoms occurs.
- other dosage regimens may be useful. The progress of this therapy is easily monitored by conventional techniques and assays.
- the polypeptide variant composition will be formulated, dosed, and administered in a fashion consistent with good medical practice. Factors for consideration in this context include the particular disorder being treated, the particular mammal being treated, the clinical condition of the individual patient, the cause of the disorder, the site of delivery of the agent, the method of administration, the scheduling of administration, and other factors known to medical practitioners.
- the "therapeutically effective amount" of the polypeptide variant to be administered will be governed by such considerations, and is the minimum amount necessary to prevent, ameliorate, or treat a disease or disorder.
- the polypeptide variant need not be, but is optionally formulated with one or more agents currently used to prevent or treat the disorder in question.
- the effective amount of such other agents depends on the amount of polypeptide variant present in the formulation, the type of disorder or treatment, and other factors discussed above. These are generally used in the same dosages and with administration routes as used hereinbefore or about from 1 to 99% of the heretofore employed dosages.
- the invention will be more fully understood by reference to the following examples. They should not, however, be construed as limiting the scope of this invention. All literature and patent citations mentioned herein are expressly incorporated by reference.
- This assay determines binding of an IgG Fc region to recombinant Fc ⁇ RIIA, Fc ⁇ RIIB and Fc ⁇ RIIIA ⁇ subunits expressed as His6-glutathione S transferase (GST)-tagged fusion proteins. Since the affinity of the Fc region of IgG 1 for the Fc ⁇ RI is in the nanomolar range, the binding of IgGI Fc variants can be measured by titrating monomeric IgG and measuring bound IgG with a polyclonal anti-lgG in a standard ELISA format (Example 2 below). The affinity of the other members of the Fc ⁇ R family, i.e. Fc ⁇ RIIA, Fc ⁇ RIIB and Fc ⁇ RIIIA for IgG is however in the micromolar range and binding of monomeric IgGI for these receptors can not be reliably measured in an ELISA format.
- the following assay utilizes Fc variants of recombinant anti-lgE E27 ( Figures 4A and 4B) which, when mixed with human IgE at a 1 :1 molar ratio, forms a stable hexamer consisting of three anti-lgE molecules and three IgE molecules.
- a recombinant chimeric form of IgE (chimeric IgE) was engineered and consists of a human IgE Fc region and the Fab of an anti-VEGF antibody (Presta etal. Cancer Research 57:4593-4599 (1997)) which binds two VEGF molecules per mole of anti-VEGF.
- VEGF vascular endothelial growth factor
- hexamers When recombinant human VEGF is added at a 2:1 molar ratio to chimeric lgE:E27 hexamers, the hexamers are linked into larger molecular weight complexes via the chimeric IgE Fab:VEGF interaction.
- the E27 component of this complex binds to the Fc ⁇ RIIA, Fc ⁇ RIIB and Fc ⁇ RIIIA ⁇ subunits with higher avidity to permit detection in an ELISA format.
- Receptor Coat Fc ⁇ receptor ⁇ subunits were expressed as GST fusions of His6 tagged extracellular domains (ECDs) in 293 cells resulting in an ECD-6His-GST fusion protein (Graham etal. J. Gen . Virol. 36:59-74 (1977) and Gorman et al. DNA Prot. Eng. Tech. 2:3-10 (1990)) and purified by Ni-NTA column chromatography (Qiagen, Australia) and buffer exchanged into phosphate buffered saline (PBS). Concentrations were determined by absorption at 280nm using extinction coefficients derived by amino acid composition analysis. Receptors were coated onto Nunc F96 maxisorb plates (cat no.
- Immune Complex Formation Equal molar amounts (1 :1) of E27 and recombinant chimeric IgE which binds two moles recombinant human VEGF per mole of chimeric IgE are added to a 12 x 75mm polypropylene tube in PBS and mixed by rotation for 30 minutes at 25°C.
- E27 (anti-lgE) /chimeric IgE (IgE) hexamers are formed during this incubation.
- Recombinant human VEGF (165 form, MW 44,000) is added at a 2:1 molar ratio to the IgE concentration and mixed by rotation an additional 30 minutes at 25°C.
- VEGF- chimeric IgE binding links 165 form, MW 44,000
- E27 -chimeric lgE:VEGF: (1 :1:2 molar ratio) complexes are added to Fc ⁇ R ⁇ subunit coated plates at E27 concentrations of 5 ⁇ g and 1 ⁇ g total IgG in quadruplicate in assay buffer and incubated for 120 minutes at 25°C on an orbital shaker.
- HRP horse radish peroxidase conjugated goat anti-human IgG ( ⁇ ) heavy chain specific
- Plates are washed 5x with wash buffer to remove unbound HRP goat anti-human IgG and bound anti-lgG is detected by adding 100 ⁇ l of substrate solution (0.4mg/ml o-phenylenedaimine dihydrochloride, Sigma P6912, 6 mM H 2 0 2 in PBS) and incubating for 8 min at 25°C. Enzymatic reaction is stopped by the addition of 100 ⁇ l 4.5N H 2 S0 4 and colorimetric product is measured at 490 nm on a 96 well plate densitometer (Molecular Devices). Binding of E27 variant complexes is expressed as a percent of the wild type E27 containing complex.
- EXAMPLE 2 Identification of Unique C1q Binding Sites in a Human IgG Antibody
- mutations were identified in the CH2 domain of a human IgGI antibody, "C2B8" (Reff et al., Blood 83:435 (1994)), that ablated binding of the antibody to C1q but did not alter the conformation of the antibody nor affect binding to each of the Fc ⁇ Rs.
- C2B8 Reff et al., Blood 83:435 (1994)
- ablated binding of the antibody to C1q but did not alter the conformation of the antibody nor affect binding to each of the Fc ⁇ Rs.
- alanine scanning mutagenesis five variants in human IgGI were identified, D270K, D270V, K322A P329A, and P331 , that were non-lytic and had decreased binding to C1q.
- the heavy and light chain plasmids were co- transfected into an adenovirus transformed human embryonic kidney cell line as previously described (Werther etal., J. Immunol. 157:4986 (1996)). The media was changed to serum-free 24 hours after transfection and the secreted antibody was harvested after five days.
- the antibodies were purified using Protein A-SEPHAROSE CL-4BTM (Pharmacia), buffer exchanged and concentrated to 0.5 ml with PBS using a Centricon-30 (Amicon), and stored at 4°C. The concentration of the antibody was determined using total Ig-binding ELISA.
- C1q Binding ELISA Costar 96 well plates were coated overnight at 4°C with the indicated concentrations of C2B8 in coating buffer (0.05 M sodium carbonate buffer), pH 9. The plates were then washed 3x with PBS/ 0.05% TWEEN 20TM, pH 7.4 and blocked with 200 ⁇ l of ELISA diluent without thimerosal (0.1 M NaP04 / 0.1 M NaCl / 0.1% gelatin / 0.05% TWEEN 20TM/ 0.05% ProClin300) for 1 hr at room temperature.
- the plate was washed 3x with wash buffer, an aliquot of 100 ⁇ l of 2 ⁇ g/ml C1q (Quidel, San Diego, CA) was added to each well and incubated for 2 hrs at room temperature. The plate was then washed 6x with wash buffer. 100 ⁇ l of a 1 : 1000 dilution of sheep anti-complement C1q peroxidase conjugated antibody (Biodesign) was added to each well and incubated for 1 hour at room temperature. The plate was again washed 6x with wash buffer and 100 ⁇ l of substrate buffer (PBS/0.012% H 2 0 2 ) containing OPD (O-phenylenediamine dihydrochloride (Sigma)) was added to each well.
- substrate buffer PBS/0.012% H 2 0 2
- OPD O-phenylenediamine dihydrochloride
- the oxidation reaction observed by the appearance of a yellow color, was allowed to proceed for 30 minutes and stopped by the addition of 100 ⁇ l of 4.5 N H 2 S0 4 .
- the absorbance was then read at (492-405) nm using a microplate reader (SPECTRA MAX 250TM, Molecular Devices Corp.).
- the appropriate controls were run in parallel (i.e. the ELISA was performed without C1q for each concentration of C2B8 used and also the ELISA was performed without C2B8).
- C1q binding was measured by plotting the absorbance (492-405) nm versus concentration of C2B8 in ⁇ g/ml using a 4-parameter curve fitting program (KALEIDAGRAPHTM) and comparing EC 50 values.
- CDC Complement Dependent Cytotoxicity Assay. This assay was performed essentially as previously described (Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996)). Various concentrations of C2B8 (0.08-20 ⁇ g/ml) were diluted with RHB buffer (RPMI 1640/20mM HEPES (pH 7.2)/2mM Glutamine/0.1% BSA/100 ⁇ g/ml Gentamicin). Human complement (Quidel) was diluted 1 :3 in RHB buffer and WIL2-S cells (available from the ATCC,
- Manassas, VA which express the CD20 antigen were diluted to a density of 1 x 10 6 cells /ml with
- CD20 Binding Potency of the C2B8 Variants The binding of C2B8 and variants to the CD20 antigen were assessed by a method previously described (Reff et al., (1994), supra; reviewed in Gazzano-Santoro etal., (1996), supra). WIL2-S cells were grown for 3-4 days to a cell density of 1 x 10 6 cells/ml. The cells were washed and spun twice in FACS buffer (PBS/0.1% BSA/0.02% NaN 3 ) and resuspended to a cell density of 5 x 10 6 cells/ml.
- FACS buffer PBS/0.1% BSA/0.02% NaN 3
- Fc ⁇ RI ⁇ subunit-GST fusion was coated onto Nunc F96 maxisorb plates (cat no. 439454) by adding 100 ⁇ l of receptor-GST fusion at 1 ⁇ g/ml in PBS and incubated for 48 hours at 4°C. Prior to assay, plates are washed 3x with 250 ⁇ l of wash buffer (PBS pH 7.4 containing 0.5% TWEEN 20TM) and blocked with 250 ⁇ l of assay buffer (50mM Tris buffered saline, 0.05% TWEEN 20TM, 0.5% RIA grade bovine albumin (Sigma A7888), and 2mM EDTA pH 7.4).
- wash buffer PBS pH 7.4 containing 0.5% TWEEN 20TM
- assay buffer 50mM Tris buffered saline, 0.05% TWEEN 20TM, 0.5% RIA grade bovine albumin (Sigma A7888), and 2mM EDTA pH 7.4
- Plates are washed 5x with wash buffer to remove unbound HRP goat anti-human IgG and bound anti-lgG is detected by adding 100 ⁇ l of substrate solution (0.4mg/ml o- phenylenedaimine dihydrochloride, Sigma P6912, 6 mM H 2 0 2 in PBS) and incubating for 8 min at 25°C. Enzymatic reaction is stopped by the addition of 100 ⁇ l 4.5N H 2 S0 4 and colorimetric product is measured at 490 nm on a 96 well plate densitometer (Molecular Devices). Binding of variant is expressed as a percent of the wild type molecule.
- Fc ⁇ RII and III binding ELISAs were performed as described in Example 1 above.
- ELISA plates were coated with 2 ⁇ g/ml streptavidin (Zymed, South San Francisco) in 50 mM carbonate buffer, pH 9.6, at 4°C overnight and blocked with PBS-0.5% BSA, pH 7.2 at room temperature for one hour.
- Biotinylated FcRn prepared using biotin-X-NHS from Research Organics, Cleveland, OH and used at 1-2 ⁇ g/ml
- PBS-0.5% BSA 0.05% polysorbate 20, pH 7.2
- the human IgGI of C2B8 was substituted for human lgG2 and used as a negative control in the C1q binding studies.
- the lgG2 variant appears to have a much lower affinity for C1q than the E318A and K320A variants (Fig. 2).
- the results demonstrate that E318 and K320 do not constitute the core C1q binding sites for human IgGI .
- the K322A substitution had a significant effect on both complement activity and C1q binding.
- the K322A variant did not have CDC activity when tested in the above CDC assay and was more than a 100 fold lower than wild type C2B8 in binding to C1q (Fig. 2).
- K322 is the only residue of the proposed core C1q binding sites that appeared to have a significant effect on complement activation and C1q binding.
- K334A, and T335A were assessed for their ability to bind C1q and also to activate complement.
- the P329A and the P331A variants did not activate complement and had decreased binding to C1q.
- the P331A variant did not activate complement and was 60 fold lower in binding to C1q (Fig. 3) when compared to wild type C2B8 (Fig. 2).
- the concentration range of the antibody variants used in Fig. 3 is expanded to 100 ⁇ g/ml in order to observe saturation of C1q binding to the P331 A variant.
- the mutation P329A results in an antibody that does not activate complement and is more than a 100 fold lower in binding to C1q (Fig. 3) when compared to wild type C2B8 (Fig. 2).
- Variants that did not bind to C1q and hence did not activate complement were examined for their ability to bind to the Fc receptors: Fc ⁇ RI, Fc ⁇ RIIA, Fc ⁇ RIIB, Fc ⁇ RIIIA and FcRn.
- This particular study was performed using a humanized anti-lgE antibody, an IgGI antibody with these mutations (see Example 1 above).
- a further residue involved in binding human C1q was identified using the methods described in the present example.
- the residue D270 was replaced with lysine and valine to generate variants D270K and D270V, respectively. These variants both showed decreased binding to human C1q (Fig. 6) and were non-lytic (Fig. 7).
- the two variants bound the CD20 antigen normally and recruited ADCC.
- K326, A327, E333 and K334 are potential sites for improving the efficacy of antibodies by way of the CDC pathway.
- the aim of this study was to improve CDC activity of an antibody by increasing binding to C1q.
- a further control antibody wild type C2B8 produced in Chinese hamster ovary (CHO) cells essentially as described in US Patent 5,736,137, was included in a C1q binding ELISA to confirm that wt C2B8 produced in the 293 kidney cell line had the same C1q binding activity as the CHO- produced antibody (see "CHO-wt-C2B8" in Fig. 8).
- CD20 binding potency assay in this example were performed as described in Example 2 above.
- K326A, K326D, K326E, K326G, K326V, K326M and K326W were K326A, K326D, K326E, K326G, K326V, K326M and K326W. As shown in Fig. 9, these variants all bound to C1q with a better affinity than the wild type antibody. K326W, K326M, K326D and K326E showed at least a two-fold increase in binding to C1q (Table 5). Among the K326 variants, K326W had the best affinity for C1q.
- E333 was also substituted with other amino acid residues.
- E333S, E333G, E333V, E333D, and E333Q all had increased binding to C1q when compared to the wild type (Fig. 11 ).
- the order of binding affinity for C1 q was as follows: E333S>E333A>E333G>E333V>E333D>E333Q.
- Substitutions with amino acid residues with small side chain volumes, i.e. serine, alanine and glycine resulted in variants with higher affinity for C1q in comparison to the other variants, E333V, E333D and E333Q, with larger side chain volumes.
- the variant E333S had the highest affinity for C1q, showing a two-fold increase in binding when compared to the wild type. Without being bound to any one theory, this indicates the effect on C1q binding at 333 may also be due in part to the polarity of the residue.
- Double variants were also generated. As shown in Figs. 12 and 13, double variants
- K326M-E333S and K326A-E333A were at least three-fold better at binding human C1q than wild type C2B8 (Fig. 12) and at least two-fold better at mediating CDC compared to wild type C2B8 (Fig. 13). Additivity indicates these are independently acting variants.
- EXAMPLE 4 Identification of FcR Binding Sites in Human IgG Antibodies in the present study, the effect of mutating various Fc region residues of an IgGI antibody with respect to binding Fc ⁇ RI, Fc ⁇ RIIA, Fc ⁇ RIIB and Fc ⁇ RIIIIA as well as FcRn was evaluated. Antibody variants with improved as well as diminished FcR binding were identified.
- IgGI Variants Recombinant anti-lgE E27 having the light chain and heavy chain sequences in Figs. 4A and 4B, respectively, was used as the parent antibody in the following experiments. This antibody binds the antigen IgE and has a non-A allotype IgGI Fc region. By site directed mutagenesis (Kunkel etal., Proc. Natl. Acad.Sci.USA 82:488 (1987)), variants of the Fc region in the heavy chain of the above parent antibody were constructed. The heavy and light chain plasmids were co-transfected into an adenovirus transformed human WO 00/42072 PCT/TJSOO/00973
- Fc ⁇ RIA was expressed as a GST fusion of His6 tagged extracellular domain in 293 cells and purified by Ni-NTA column chromatography.
- Protein was concentrated to 0.5 mL and buffer exchanged into PBS. Concentrations were determined by adsorption at 280 nm using an extinction coefficient derived by amino acid composition analysis. Purified receptors were coated onto Nunc F96 maxisorb plates (cat no. 439545) at approximately 150 ng per well by adding 100 ⁇ L of receptor at 1.5 ⁇ g/mL in PBS and incubated for 24 hours at 4°C.
- E27 100 ⁇ L of E27 was added to the first four wells of the Fc ⁇ RIA subunit coated plated at a concentration of 10 ⁇ g/mL. 80 ⁇ L of assay buffer was added to the next four well followed by 20 ⁇ Lof the 10 ⁇ g/mL E27 IgG to give a final concentration of 2 ⁇ g/mL. Plates were incubated at
- FcyRIA THP-1 Assay 100 ⁇ L of E27 was added to the first three wells of a serocluster plate (Costar) at a concentration of 20 ⁇ g/mL in assay buffer (1x PBS, 0.1% BSA, 0.01% NaN 3 ). 92.5 ⁇ L of assay buffer was added to the next three wells followed by 7.5 ⁇ L of the 20 ⁇ g/mL E27 IgG to give a final concentration of 1.5 ⁇ g/mL. To each well, 100 ⁇ L of THP-1 cells were added at a concentration of 5 million cells/mL in FACS assay buffer. The plate is incubated on ice for 30 minutes
- FITC conjugated F(ab') 2 fragment of goat anti- human IgG heavy chain specific was detected by adding 100 ⁇ L FITC conjugated F(ab') 2 fragment of goat anti- human IgG heavy chain specific. (Jackson Immunoresearch) at 1 :200. FITC conjugates were incubated with cells for 30 minutes on ice. Cells were washed x3 with assay buffer to remove unbound FITC conjugate. Cells were stained with P.I. (SIGMA) at 2.5 ⁇ g/mL and analyzed by flow cytometry.
- SIGMA P.I.
- Binding of E27 variants at IgG concentration of 1.5 ⁇ g/mL was expressed as a ratio of wild type E27.
- Fc ⁇ RIIA, Fc ⁇ RIIB and Fc ⁇ RIIIA binding ELISAs were performed as described in Example 1 above, with detection of the stable hexamer (consisting of three anti-lgE molecules and three IgE molecules).
- FcRn Binding ELISA For measuring FcRn binding activity of IgG variants, ELISA plates were coated with 2 ⁇ g/ml streptavidin (Zymed, South San Francisco) in 50 mM carbonate buffer, pH 9.6, at 4°C overnight and blocked with PBS-0.5% BSA, pH 7.2 at room temperature for one hour. Biotinylated FcRn (prepared using biotin-X-NHS from Research Organics, Cleveland, OH and used at 1-2 ⁇ g/ml) in PBS-0.5% BSA, 0.05% polysorbate 20, pH 7.2, was added to the plate and incubated for one hour.
- IgG standard 1.6-100 ng/ml
- PBS-0.5% BSA, 0.05% polysorbate 20, pH 6.0 Two fold serial dilutions of IgG standard (1.6-100 ng/ml) or variants in PBS-0.5% BSA, 0.05% polysorbate 20, pH 6.0, were added to the plate and incubated for two hours. Bound IgG was detected using peroxidase labeled goat F(ab') 2 anti-human IgG F(ab') 2 in the above pH 6.0 buffer (Jackson ImmunoResearch, West Grove, PA) followed by 3,3',5,5'- tetramethyl benzidine (Kirgaard & Perry Laboratories) as the substrate. Plates were washed WO 00/42072 PCT/TJSOO/00973
- chromium 51 -labeled target cells tumor cell lines were grown in tissue culture plates and harvested using sterile 10 mM EDTA in PBS.
- SK-BR-3 cells a 3+ HER2-overexpressing human breast cancer cell line, were used as targets in all assays.
- the detached cells were washed twice with cell culture medium.
- Cells (5x10 6 ) were labeled with 200 ⁇ Ci of chromium51(New England Nuclear/DuPont) at 37°C for one hour with occasional mixing. Labeled cells were washed three times with cell culture medium, then were resuspended to a concentration of 1x10 5 cells/mL.
- Cells were used either without opsonization, or were opsonized prior to the assay by incubation with rhuMAb HER2 wildtype (HERCEPTIN ® ) or seven Fc mutants (G14, G18, G17, G36, G30, G31 and G34) at 100 ng/mL and 1.25 ng/mL in PBMC assay or 20 ng/mL and 1 ng/mL in NK assay.
- rhuMAb HER2 wildtype HERCEPTIN ®
- Fc mutants G14, G18, G17, G36, G30, G31 and G34
- Peripheral blood mononuclear cells were prepared by collecting blood on heparin from normal healthy donors and dilution with an equal volume of phosphate buffered saline (PBS). The blood was then layered over LYMPHOCYTE SEPARATION MEDIUM® (LSM: Organon Teknika) and centrifuged according to the manufacturer's instructions. Mononuclear cells were collected from the LSM-plasma interface and were washed three times with PBS. Effector cells were suspended in cell culture medium to a final concentration of 1x10 7 cells/mL.
- PBS phosphate buffered saline
- NK cells natural killer cells were isolated from PBMCs by negative selection using an NK cell isolation kit and a magnetic column (Miltenyi Biotech) according to the manufacturer's instructions. Isolated NK cells were collected, washed and resuspended in cell culture medium to a concentration of 2x10 6 cells/mL. The identity of the NK cells was confirmed by flow cytometric analysis.
- Varying effecto ⁇ target ratios were prepared by serially diluting the effector (either PBMC or NK) cells two-fold along the rows of a microtiter plate (100 ⁇ L final volume) in cell culture medium.
- the concentration of effector cells ranged from 1.0x10 7 /mL to 2.0 x 10 4 /mL for PBMC and from 2.0x10 6 /mL to 3.9x10 3 /mL for NK.
- 100 ⁇ L of chromium 51- labeled target cells (opsonized or nonoponsonized) at 1x10 5 cells/mL were added to each well of the plate.
- % Cytotoxicity (sample cpm-spontaneous lysis)/(total lysis-spontaneous lysis) x 100 Four-parameter curve-fitting was then used to evaluate the data (KaleidaGraph 3.0.5).
- BIO T359'(382) 1.04 1.04 (0.05) 3 1.13 (0.10) 1.15 (0.04) 1.23 (0.26) n 3
- Variants with increased binding to a Fc ⁇ R generally had binding values ⁇ 1.20 as determined in this Example and those with reduced binding to a Fc ⁇ R generally had binding values ⁇ 0.80 as determined in this Example.
- Variants with increased binding to FcRn generally had binding values ⁇ 1.30 as determined in this Example and those with reduced binding to FcRn generally had binding values ⁇ 0.70 as determined in this Example.
- This study includes a complete mapping of human IgGI for human Fc ⁇ RI, Fc ⁇ RIIA, Fc ⁇ RIIB, Fc ⁇ RIIIA, and FcRn.
- Fc ⁇ RI and FcRn are high affinity receptors and monomeric IgG could be evaluated in the assays for these two receptors.
- Fc ⁇ RIIA, Fc ⁇ RIIB and Fc ⁇ RIIIA are low affinity receptors and required use of an immune complex.
- an ELISA-type assay was used for Fc ⁇ RIIA, Fc ⁇ RIIB, and Fc ⁇ RIIIA, in which pre-formed hexamers, consisting of three anti-lgE E27 and three IgE molecules were bound to the Fc ⁇ R and either anti-human IgG Fc-HRP or protein G-HRP used as detection reagent.
- these hexamers could be linked into multimers by addition of human VEGF (using anti-VEGF IgE).
- the hexameric complexes were used since these provided sufficient binding and required less IgG. Complexes formed using other antibody:antigen combinations are also possible reagents, as long as the antigen contains at least two identical binding sites per molecule for the antibody.
- VEGF contains two binding sites per VEGF dimer for anti-VEGF A.4.6.1 (Kim et al., Growth Factors 7:53 (1992) and Kim et al. Nature 362:841 (1993)). VEGF:anti-VEGF multimers also bound to the low affinity Fc ⁇ RIIA and Fc ⁇ RIIIA (Figs. 16A and 16B).
- alanine variants were found. Some variants exhibited reduced binding to all Fc ⁇ R (G14, Fig. 17), while other variants showed reduced binding only to one Fc ⁇ R (G36, Fig. 17), improved binding only to one Fc ⁇ R (G15, G54, G55, Fig. 17), or simultaneous reduction to one Fc ⁇ R with improvement to another (G16, Fig. 17).
- One application of these variants is to improve the ADCC effector function of an antibody. This can be achieved by modifying Fc region amino acids at one or more residues which would lead to improved binding to Fc ⁇ RIIIA. Improved Fc ⁇ RIIIA binding would lead to improved binding by NK cells, which carry only Fc ⁇ RIIIA and can mediate ADCC.
- Selected alanine variants which were either reduced in binding to Fc ⁇ RIIIA (variants 17, 18, 34; Table 6), had no effect on Fc ⁇ RIIIA binding (variant 31 ; Table 6), or had improved binding to Fc ⁇ RIIIA (variants 30, 36; Table 6) were tested in an in vitro ADCC assay using human PBMCs as effector cells.
- the IgG Fc variants used in this assay were generated by substituting the V H /V L domains of anti-lgE E27 with those from anti-HER2 antibody; HERCEPTIN® (humAb4D5-8 in Table 1 of Carter etal. PNAS (USA) 89:4285-4289 (1992)).
- the pattern of ADCC exhibited by the variants correlated well with the pattern of binding to Fc ⁇ RIIIA (Figs. 20 and 21).
- variant 36 S298(317)A also showed improvement in ADCC compared to wildtype HERCEPTIN® at 1.25 ng/ml (Fig. 21 ).
- the pattern of binding of the selected IgGI variants to the relatively higher affinity Fc ⁇ RIIIA-V158 was the same as for the relatively lower affinity Fc ⁇ RIIIA-F158 (the F158 form was used in assaying all variants).
- IgGI variants which showed improved binding to the Fc ⁇ RIIIA-F158 form also showed improved binding to the Fc ⁇ RIIIA-V158 form though the improvement was not as pronounced.
- Fc ⁇ RIIA-R131 used in assaying all variants
- Fc ⁇ RIIA-H131 the binding pattern of the selected IgGI variants did show some distinct differences.
- S267(280)A, H268(281)A, and S267(280)A/H268(281)A exhibited improved binding to Fc ⁇ RIIA-R131, compared to native IgGI, but not to Fc ⁇ RIIA-H131.
- S267(280)G showed improved binding to Fc ⁇ RIIA-R131 but reduced binding to Fc ⁇ RIIA-H131 (Table 10).
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JP2000593638A JP2003512019A (en) | 1999-01-15 | 2000-01-14 | Polypeptide variants with altered effector functions |
EP00906925.3A EP1141024B1 (en) | 1999-01-15 | 2000-01-14 | POLYPEPTIDE COMPRISING A VARIANT HUMAN IgG1 Fc REGION |
AU28505/00A AU778683B2 (en) | 1999-01-15 | 2000-01-14 | Polypeptide variants with altered effector function |
MXPA04011973A MX353234B (en) | 1999-01-15 | 2000-01-14 | Polypeptide variants with altered effector function. |
CA2359067A CA2359067C (en) | 1999-01-15 | 2000-01-14 | Polypeptide variants with altered effector function |
ES00906925.3T ES2694002T3 (en) | 1999-01-15 | 2000-01-14 | Polypeptide comprising an Fc region of variant human IgG1 |
KR1020107006514A KR101155191B1 (en) | 1999-01-15 | 2000-01-14 | Polypeptide Variants with Altered Effector Function |
BR0008758-0A BR0008758A (en) | 1999-01-15 | 2000-01-14 | Variants of parental polypeptides with altered effector function, polypeptides, isolated nucleic acid composition, vector, host cell, method for producing a polypeptide variant, method for treating a disorder in mammals and method for producing a variant fc region |
IL14405600A IL144056A0 (en) | 1999-01-15 | 2000-01-14 | Polypeptide variants with altered effector function |
HU1500355A HU230769B1 (en) | 1999-01-15 | 2000-01-14 | Polypeptide variants with altred effector function |
MXPA01007170A MXPA01007170A (en) | 1999-01-15 | 2000-01-14 | Polypeptide variants with altered effector function. |
HU0104865A HUP0104865A3 (en) | 1999-01-15 | 2000-01-14 | Polypeptide variants with altered effector function |
IL144056A IL144056A (en) | 1999-01-15 | 2001-06-28 | Polypeptide variants with altered effector function |
AU2008229968A AU2008229968B2 (en) | 1999-01-15 | 2008-10-16 | Polypeptide variants with altered effector function |
IL222149A IL222149B (en) | 1999-01-15 | 2012-09-27 | A polypeptide comprising a variant human igg fc region that has increased fcrn binding affinity |
IL223047A IL223047A (en) | 1999-01-15 | 2012-11-15 | Antibody comprising an fc region and uses thereof |
IL223048A IL223048A (en) | 1999-01-15 | 2012-11-15 | Polypeptide variants that bind fcrn with increased binding affinity and methods for their preparation |
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US7371826B2 (en) | 1999-01-15 | 2008-05-13 | Genentech, Inc. | Polypeptide variants with altered effector function |
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WO2011020049A1 (en) | 2009-08-14 | 2011-02-17 | Genentech, Inc. | Biological markers for monitoring patient response to vegf antagonists |
WO2011022264A1 (en) | 2009-08-15 | 2011-02-24 | Genentech, Inc. | Anti-angiogenesis therapy for the treatment of previously treated breast cancer |
WO2011021146A1 (en) | 2009-08-20 | 2011-02-24 | Pfizer Inc. | Osteopontin antibodies |
EP2292264A2 (en) | 2003-07-24 | 2011-03-09 | Innate Pharma | Methods and compositions for increasing the efficiency of therapeutic antibodies using NK cell potentiating compounds |
WO2011028950A1 (en) | 2009-09-02 | 2011-03-10 | Genentech, Inc. | Mutant smoothened and methods of using the same |
EP2295080A2 (en) | 2005-07-25 | 2011-03-16 | Trubion Pharmaceuticals, Inc. | B-cell reduction using CD37-specific and CD20-specific binding molecules |
WO2011032013A1 (en) | 2009-09-11 | 2011-03-17 | Genentech, Inc. | Method to identify a patient with an increased likelihood of responding to an anti-cancer agent |
WO2011029823A1 (en) | 2009-09-09 | 2011-03-17 | Novartis Ag | Monoclonal antibody reactive with cd63 when expressed at the surface of degranulated mast cells |
WO2011033006A1 (en) | 2009-09-17 | 2011-03-24 | F. Hoffmann-La Roche Ag | Methods and compositions for diagnostics use in cancer patients |
US7914785B2 (en) | 2008-01-02 | 2011-03-29 | Bergen Teknologieverforing As | B-cell depleting agents, like anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome |
WO2011044368A1 (en) | 2009-10-07 | 2011-04-14 | Macrogenics, Inc. | Fc region-containing polypeptides that exhibit improved effector function due to alterations of the extent of fucosylation, and methods for their use |
US7930107B2 (en) | 2003-12-04 | 2011-04-19 | Xencor, Inc. | Methods of generating variant proteins with increased host string content |
WO2011047083A1 (en) | 2009-10-13 | 2011-04-21 | Oxford Biotherapeutics Ltd. | Antibodies against epha10 |
WO2011050188A1 (en) | 2009-10-22 | 2011-04-28 | Genentech, Inc. | Anti-hepsin antibodies and methods using same |
WO2011053982A2 (en) | 2009-11-02 | 2011-05-05 | University Of Washington | Therapeutic nuclease compositions and methods |
WO2011053465A1 (en) | 2009-10-14 | 2011-05-05 | Kalobios Pharmaceuticals, Inc. | Antibodies to epha3 |
WO2011056497A1 (en) | 2009-10-26 | 2011-05-12 | Genentech, Inc. | Activin receptor type iib compositions and methods of use |
WO2011056772A1 (en) | 2009-11-04 | 2011-05-12 | Schering Corporation | Engineered anti-tslp antibody |
WO2011056502A1 (en) | 2009-10-26 | 2011-05-12 | Genentech, Inc. | Bone morphogenetic protein receptor type ii compositions and methods of use |
WO2011056494A1 (en) | 2009-10-26 | 2011-05-12 | Genentech, Inc. | Activin receptor-like kinase-1 antagonist and vegfr3 antagonist combinations |
WO2011057120A1 (en) | 2009-11-05 | 2011-05-12 | Genentech, Inc. | Methods and composition for secretion of heterologous polypeptides |
WO2011054030A1 (en) | 2009-11-05 | 2011-05-12 | Cephalon Australia Pty Ltd | Treatment of cancer involving mutated kras or braf genes |
WO2011060015A1 (en) | 2009-11-11 | 2011-05-19 | Genentech, Inc. | Methods and compositions for detecting target proteins |
WO2011067711A2 (en) | 2009-12-01 | 2011-06-09 | Compugen Ltd | Novel heparanase splice variant |
WO2011068993A1 (en) | 2009-12-02 | 2011-06-09 | Acceleron Pharma Inc. | Compositions and methods for increasing serum half-life of fc fusion proteins. |
WO2011071577A1 (en) | 2009-12-11 | 2011-06-16 | Genentech, Inc. | Anti-vegf-c antibodies and methods using same |
WO2011076781A1 (en) | 2009-12-22 | 2011-06-30 | Novartis Ag | Tetravalent cd47-antibody constant region fusion protein for use in therapy |
WO2011079185A1 (en) | 2009-12-23 | 2011-06-30 | Genentech, Inc. | Anti-bv8 antibodies and uses thereof |
US7981414B2 (en) | 2005-12-20 | 2011-07-19 | Cephalon Australia Pty Ltd | Anti-inflammatory dAb |
WO2011100403A1 (en) | 2010-02-10 | 2011-08-18 | Immunogen, Inc | Cd20 antibodies and uses thereof |
WO2011098449A1 (en) | 2010-02-10 | 2011-08-18 | Novartis Ag | Methods and compounds for muscle growth |
WO2011106300A2 (en) | 2010-02-23 | 2011-09-01 | Genentech, Inc. | Anti-angiogenesis therapy for the treatment of ovarian cancer |
WO2011109400A2 (en) | 2010-03-04 | 2011-09-09 | Macrogenics,Inc. | Antibodies reactive with b7-h3, immunologically active fragments thereof and uses thereof |
WO2011108502A1 (en) | 2010-03-02 | 2011-09-09 | 協和発酵キリン株式会社 | Modified antibody composition |
EP2366716A2 (en) | 2006-03-21 | 2011-09-21 | Genentech, Inc. | Combinatorial therapy involving alpha5beta1 antagonists |
WO2011122011A2 (en) | 2010-03-30 | 2011-10-06 | Chugai Seiyaku Kabushiki Kaisha | Antibodies with modified affinity to fcrn that promote antigen clearance |
US8039596B2 (en) | 2008-02-05 | 2011-10-18 | Bristol-Myers Squibb Company | Alpha 5-beta 1 antibodies and their uses |
EP2383295A1 (en) | 2003-12-10 | 2011-11-02 | Medarex, Inc. | IP-10 antibodies and their uses |
WO2011138392A1 (en) | 2010-05-06 | 2011-11-10 | Novartis Ag | Compositions and methods of use for therapeutic low density lipoprotein -related protein 6 (lrp6) antibodies |
WO2011138391A1 (en) | 2010-05-06 | 2011-11-10 | Novartis Ag | Compositions and methods of use for therapeutic low density lipoprotein - related protein 6 (lrp6) multivalent antibodies |
WO2011146568A1 (en) | 2010-05-19 | 2011-11-24 | Genentech, Inc. | Predicting response to a her inhibitor |
US8067002B2 (en) | 2006-11-02 | 2011-11-29 | Genentech, Inc. | Humanized anti-factor D antibodies |
WO2011153224A2 (en) | 2010-06-02 | 2011-12-08 | Genentech, Inc. | Diagnostic methods and compositions for treatment of cancer |
WO2011153346A1 (en) | 2010-06-03 | 2011-12-08 | Genentech, Inc. | Immuno-pet imaging of antibodies and immunoconjugates and uses therefor |
WO2011153243A2 (en) | 2010-06-02 | 2011-12-08 | Genentech, Inc. | Anti-angiogenesis therapy for treating gastric cancer |
EP2395024A2 (en) | 2005-08-26 | 2011-12-14 | GlycArt Biotechnology AG | Modified antigen binding molecules with altered cell signaling activity |
US8084582B2 (en) | 2003-03-03 | 2011-12-27 | Xencor, Inc. | Optimized anti-CD20 monoclonal antibodies having Fc variants |
EP2399605A1 (en) | 2005-02-23 | 2011-12-28 | Genentech, Inc. | Extending time to disease progression or survival in cancer patients |
EP2402373A2 (en) | 2006-01-05 | 2012-01-04 | Genentech, Inc. | Anti-EphB4 Antibodies and Methods Using Same |
WO2012006633A1 (en) | 2010-07-09 | 2012-01-12 | Biogen Idec Hemophilia Inc. | Chimeric clotting factors |
WO2012010550A1 (en) | 2010-07-19 | 2012-01-26 | F. Hoffmann-La Roche Ag | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
WO2012012750A1 (en) | 2010-07-23 | 2012-01-26 | Trustees Of Boston University | ANTI-DEsupR INHIBITORS AS THERAPEUTICS FOR INHIBITION OF PATHOLOGICAL ANGIOGENESIS AND TUMOR CELL INVASIVENESS AND FOR MOLECULAR IMAGING AND TARGETED DELIVERY |
WO2012010549A1 (en) | 2010-07-19 | 2012-01-26 | F. Hoffmann-La Roche Ag | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
WO2012016173A2 (en) | 2010-07-30 | 2012-02-02 | Ac Immune S.A. | Safe and functional humanized antibodies |
WO2012016203A1 (en) | 2010-07-29 | 2012-02-02 | Eleven Biotherapeutics, Inc. | Chimeric il-1 receptor type i agonists and antagonists |
EP2415483A1 (en) | 2005-07-25 | 2012-02-08 | Emergent Product Development Seattle, LLC | Single dose use of cd20-specific binding molecules |
WO2012019061A2 (en) | 2010-08-05 | 2012-02-09 | Stem Centrx, Inc. | Novel effectors and methods of use |
WO2012018687A1 (en) | 2010-08-02 | 2012-02-09 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
EP2418220A2 (en) | 2003-12-10 | 2012-02-15 | Medarex, Inc. | Interferon alpha antibodies and their uses |
EP2420512A2 (en) | 2003-08-01 | 2012-02-22 | Genentech, Inc. | Anti-VEGF antibodies |
WO2012022814A1 (en) | 2010-08-20 | 2012-02-23 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (her3) |
US8124731B2 (en) | 2002-03-01 | 2012-02-28 | Xencor, Inc. | Optimized Fc variants and methods for their generation |
WO2012027723A1 (en) | 2010-08-27 | 2012-03-01 | Stem Centrx, Inc | Notum protein modulators and methods of use |
WO2012031273A2 (en) | 2010-09-03 | 2012-03-08 | Stem Centrx, Inc. | Novel modulators and methods of use |
WO2012032080A1 (en) | 2010-09-07 | 2012-03-15 | F-Star Biotechnologische Forschungs- Und Entwicklungsges.M.B.H | Stabilised human fc |
WO2012035518A1 (en) | 2010-09-17 | 2012-03-22 | Compugen Ltd. | Compositions and methods for treatment of drug resistant multiple myeloma |
EP2433967A2 (en) | 2009-03-16 | 2012-03-28 | Cephalon Australia Pty Ltd | Humanised antibodies with anti-tumour activity |
WO2012040617A2 (en) | 2010-09-23 | 2012-03-29 | Neogenix Oncology, Inc. | Colon and pancreas cancer peptidomimetics |
WO2012041800A1 (en) | 2010-09-27 | 2012-04-05 | Morphosys Ag | Anti-cd38 antibody and lenalidomide or bortezomib for the treatment of multiple myeloma and nhl |
US8153125B2 (en) | 2003-05-20 | 2012-04-10 | Applied Molecular Evolution, Inc. | CD20 binding molecules |
WO2012045703A1 (en) | 2010-10-05 | 2012-04-12 | Novartis Ag | Anti-il12rbeta1 antibodies and their use in treating autoimmune and inflammatory disorders |
WO2012047968A2 (en) | 2010-10-05 | 2012-04-12 | Genentech, Inc. | Mutant smoothened and methods of using the same |
EP2447282A2 (en) | 2006-05-30 | 2012-05-02 | Genentech, Inc. | Anti-CD22 Antibodies, their Immunoconjugates and uses thereof |
WO2012058768A1 (en) | 2010-11-05 | 2012-05-10 | Zymeworks Inc. | Stable heterodimeric antibody design with mutations in the fc domain |
EP2452694A1 (en) | 2005-06-30 | 2012-05-16 | Janssen Biotech, Inc. | Anti-IL-23 antibodies, compositions, methods and uses |
WO2012064627A2 (en) | 2010-11-08 | 2012-05-18 | Genentech, Inc. | Subcutaneously administered anti-il-6 receptor antibody |
US8188231B2 (en) | 2002-09-27 | 2012-05-29 | Xencor, Inc. | Optimized FC variants |
WO2012069557A1 (en) | 2010-11-24 | 2012-05-31 | Glaxo Group Limited | Multispecific antigen binding proteins targeting hgf |
WO2012069433A2 (en) | 2010-11-23 | 2012-05-31 | Glaxo Group Limited | Antigen binding proteins |
WO2012071554A2 (en) | 2010-11-23 | 2012-05-31 | Alder Biopharmaceuticals, Inc. | Anti-il-6 antibodies for the treatment of oral mucositis |
US20120142593A1 (en) * | 2009-03-24 | 2012-06-07 | Bayer Healthcare Llc | Factor VIII Variants and Methods of Use |
WO2012075037A1 (en) | 2010-11-30 | 2012-06-07 | Genentech, Inc. | Low affinity blood brain barrier receptor antibodies and uses therefor |
WO2012073992A1 (en) | 2010-11-30 | 2012-06-07 | 中外製薬株式会社 | Antigen-binding molecule capable of binding to plurality of antigen molecules repeatedly |
WO2012078813A2 (en) | 2010-12-08 | 2012-06-14 | Stem Centrx, Inc. | Novel modulators and methods of use |
EP2465870A1 (en) | 2005-11-07 | 2012-06-20 | Genentech, Inc. | Binding polypeptides with diversified and consensus VH/VL hypervariable sequences |
EP2468776A2 (en) | 2007-02-09 | 2012-06-27 | Genentech, Inc. | Anti-Robo4 antibodies and uses therefor |
EP2468772A2 (en) | 2006-03-16 | 2012-06-27 | Genentech, Inc. | Antibodies to EGFL7 and methods for their use |
WO2012092539A2 (en) | 2010-12-31 | 2012-07-05 | Takeda Pharmaceutical Company Limited | Antibodies to dll4 and uses thereof |
EP2474557A2 (en) | 2007-07-16 | 2012-07-11 | Genentech, Inc. | Anti-CD79b antibodies and immunoconjugates and methods of use |
CN102596994A (en) * | 2009-08-21 | 2012-07-18 | 英国龙沙生物医药股份有限公司 | Variant immunoglobulins with improved manufacturability |
EP2486941A1 (en) | 2006-10-02 | 2012-08-15 | Medarex, Inc. | Human antibodies that bind CXCR4 and uses thereof |
WO2012112943A1 (en) | 2011-02-18 | 2012-08-23 | Stem Centrx, Inc. | Novel modulators and methods of use |
WO2012115241A1 (en) | 2011-02-25 | 2012-08-30 | 中外製薬株式会社 | Fcγriib-specific fc antibody |
WO2012118750A2 (en) | 2011-02-28 | 2012-09-07 | Genentech, Inc. | Biological markers and methods for predicting response to b-cell antagonists |
US8273352B2 (en) | 2008-04-28 | 2012-09-25 | Genentech, Inc. | Humanized anti-factor D antibodies and uses thereof |
EP2505209A1 (en) | 2006-06-26 | 2012-10-03 | MacroGenics, Inc. | Fcgamma-RIIB-specific antibodies and methods of the use thereof |
WO2012133782A1 (en) | 2011-03-30 | 2012-10-04 | 中外製薬株式会社 | Retention of antigen-binding molecules in blood plasma and method for modifying immunogenicity |
WO2012142515A2 (en) | 2011-04-13 | 2012-10-18 | Bristol-Myers Squibb Company | Fc fusion proteins comprising novel linkers or arrangements |
WO2012140627A1 (en) | 2011-04-15 | 2012-10-18 | Compugen Ltd. | Polypeptides and polynucleotides, and uses thereof for treatment of immune related disorders and cancer |
CN102746404A (en) * | 2004-11-12 | 2012-10-24 | 赞科股份有限公司 | Fc variants with altered binding to fcrn |
WO2012145493A1 (en) | 2011-04-20 | 2012-10-26 | Amplimmune, Inc. | Antibodies and other molecules that bind b7-h1 and pd-1 |
US8298533B2 (en) | 2008-11-07 | 2012-10-30 | Medimmune Limited | Antibodies to IL-1R1 |
WO2012149440A2 (en) | 2011-04-29 | 2012-11-01 | University Of Washington | Therapeutic nuclease compositions and methods |
WO2012146934A1 (en) | 2011-04-28 | 2012-11-01 | Michael Clark | Binding molecules with biased recognition |
WO2012156309A1 (en) | 2011-05-13 | 2012-11-22 | Millegen | Antibodies against her3 |
US8318907B2 (en) | 2004-11-12 | 2012-11-27 | Xencor, Inc. | Fc variants with altered binding to FcRn |
WO2012162068A2 (en) | 2011-05-21 | 2012-11-29 | Macrogenics, Inc. | Deimmunized serum-binding domains and their use for extending serum half-life |
WO2012162067A2 (en) | 2011-05-21 | 2012-11-29 | Macrogenics, Inc. | Cd3-binding molecules capable of binding to human and non-human cd3 |
WO2012162561A2 (en) | 2011-05-24 | 2012-11-29 | Zyngenia, Inc. | Multivalent and monovalent multispecific complexes and their uses |
EP2530090A2 (en) | 2006-10-19 | 2012-12-05 | CSL Limited | Anti-IL-13R alpha 1 antibodies and their uses thereof |
EP2532679A1 (en) | 2005-10-21 | 2012-12-12 | Novartis AG | Human antibodies against il13 and therapeutic uses |
EP2535355A2 (en) | 2005-03-23 | 2012-12-19 | Genmab A/S | Antibodies against CD38 for treatment of multiple myeloma |
WO2012172521A1 (en) | 2011-06-16 | 2012-12-20 | Novartis Ag | Soluble proteins for use as therapeutics |
WO2012172495A1 (en) | 2011-06-14 | 2012-12-20 | Novartis Ag | Compositions and methods for antibodies targeting tem8 |
WO2012175691A1 (en) | 2011-06-22 | 2012-12-27 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-axl antibodies and uses thereof |
WO2012175692A1 (en) | 2011-06-22 | 2012-12-27 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-axl antibodies and uses thereof |
EP2540741A1 (en) | 2006-03-06 | 2013-01-02 | Aeres Biomedical Limited | Humanized anti-CD22 antibodies and their use in treatment of oncology, transplantation and autoimmune disease |
WO2013003625A2 (en) | 2011-06-28 | 2013-01-03 | Oxford Biotherapeutics Ltd. | Antibodies |
WO2013002362A1 (en) | 2011-06-30 | 2013-01-03 | 中外製薬株式会社 | Heterodimerized polypeptide |
WO2013003680A1 (en) | 2011-06-30 | 2013-01-03 | Genentech, Inc. | Anti-c-met antibody formulations |
WO2013004842A2 (en) | 2011-07-06 | 2013-01-10 | Genmab A/S | Antibody variants and uses thereof |
WO2013006437A1 (en) | 2011-07-01 | 2013-01-10 | Novartis Ag | Method for treating metabolic disorders |
EP2548577A1 (en) | 2005-12-29 | 2013-01-23 | Janssen Biotech, Inc. | Human anti-il-23 antibodies, compositions, methods and uses |
WO2013012733A1 (en) | 2011-07-15 | 2013-01-24 | Biogen Idec Ma Inc. | Heterodimeric fc regions, binding molecules comprising same, and methods relating thereto |
WO2013010955A1 (en) | 2011-07-15 | 2013-01-24 | Morphosys Ag | Antibodies that are cross-reactive for macrophage migration inhibitory factor (mif) and d-dopachrome tautomerase (d-dt) |
WO2013011076A2 (en) | 2011-07-19 | 2013-01-24 | Glaxo Group Limited | Antigen-binding proteins with increased fcrn binding |
WO2013014208A2 (en) | 2011-07-27 | 2013-01-31 | Glaxo Group Limited | Antigen binding constructs |
WO2013025944A1 (en) | 2011-08-17 | 2013-02-21 | Genentech, Inc. | Inhibition of angiogenesis in refractory tumors |
WO2013025779A1 (en) | 2011-08-15 | 2013-02-21 | Amplimmune, Inc. | Anti-b7-h4 antibodies and their uses |
US8388955B2 (en) | 2003-03-03 | 2013-03-05 | Xencor, Inc. | Fc variants |
US8394374B2 (en) | 2006-09-18 | 2013-03-12 | Xencor, Inc. | Optimized antibodies that target HM1.24 |
EP2567709A2 (en) | 2007-11-02 | 2013-03-13 | Novartis AG | Molecules and methods for modulating low-density-lipoprotein receptor-related protein 6 (LRP6) |
WO2013039954A1 (en) | 2011-09-14 | 2013-03-21 | Sanofi | Anti-gitr antibodies |
US8409577B2 (en) | 2006-06-12 | 2013-04-02 | Emergent Product Development Seattle, Llc | Single chain multivalent binding proteins with effector function |
WO2013047729A1 (en) | 2011-09-30 | 2013-04-04 | 中外製薬株式会社 | Antigen-binding molecule inducing immune response to target antigen |
WO2013046704A2 (en) | 2011-09-30 | 2013-04-04 | Chugai Seiyaku Kabushiki Kaisha | THERAPEUTIC ANTIGEN-BINDING MOLECULE WITH A FcRn-BINDING DOMAIN THAT PROMOTES ANTIGEN CLEARANCE |
WO2013047748A1 (en) | 2011-09-30 | 2013-04-04 | 中外製薬株式会社 | Antigen-binding molecule promoting disappearance of antigens having plurality of biological activities |
WO2013047752A1 (en) | 2011-09-30 | 2013-04-04 | 中外製薬株式会社 | Antigen-binding molecule for promoting loss of antigens |
WO2013051294A1 (en) | 2011-10-05 | 2013-04-11 | 中外製薬株式会社 | Antigen-binding molecule for promoting clearance from plasma of antigen comprising saccharide chain receptor-binding domain |
WO2013054307A2 (en) | 2011-10-14 | 2013-04-18 | Novartis Ag | Antibodies and methods for wnt pathway-related diseases |
EP2586796A1 (en) | 2007-10-12 | 2013-05-01 | Novartis AG | Compositions and methods for use for antibodies against sclerostin |
EP2586788A1 (en) | 2007-07-09 | 2013-05-01 | Genentech, Inc. | Prevention of disulfide bond reduction during recombinant production of polypeptides |
WO2013059885A2 (en) | 2011-10-28 | 2013-05-02 | Cephalon Australia Pty Ltd | Polypeptide constructs and uses thereof |
WO2013067055A1 (en) | 2011-11-01 | 2013-05-10 | Bionomics, Inc. | Methods of blocking cancer stem cell growth |
WO2013067060A1 (en) | 2011-11-01 | 2013-05-10 | Bionomics, Inc. | Anti-gpr49 antibodies |
WO2013063702A1 (en) | 2011-11-04 | 2013-05-10 | Zymeworks Inc. | Stable heterodimeric antibody design with mutations in the fc domain |
WO2013067057A1 (en) | 2011-11-01 | 2013-05-10 | Bionomics, Inc. | Anti-gpr49 antibodies |
WO2013067054A1 (en) | 2011-11-01 | 2013-05-10 | Bionomics, Inc. | Antibodies and methods of treating cancer |
EP2592156A2 (en) | 2007-06-08 | 2013-05-15 | Genentech, Inc. | Gene expression markers of tumor resistance to HER2 inhibitor treatment |
US8444973B2 (en) | 2005-02-15 | 2013-05-21 | Duke University | Anti-CD19 antibodies and uses in B cell disorders |
WO2013078377A1 (en) | 2011-11-23 | 2013-05-30 | Igenica, Inc. | Anti-cd98 antibodies and methods of use thereof |
WO2013078170A1 (en) | 2011-11-21 | 2013-05-30 | Genentech, Inc. | Purification of anti-c-met antibodies |
EP2599791A1 (en) | 2007-04-27 | 2013-06-05 | Genentech, Inc. | Potent, stable and non-immunosuppressive anti-CD4 antibodies |
WO2013081143A1 (en) | 2011-11-30 | 2013-06-06 | 中外製薬株式会社 | Drug containing carrier into cell for forming immune complex |
WO2013084147A2 (en) | 2011-12-05 | 2013-06-13 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (her3) |
WO2013085972A1 (en) | 2011-12-05 | 2013-06-13 | X-Body, Inc. | Pdgf receptor beta binding polypeptides |
WO2013084148A2 (en) | 2011-12-05 | 2013-06-13 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (her3) directed to domain ii of her3 |
WO2013093762A1 (en) | 2011-12-21 | 2013-06-27 | Novartis Ag | Compositions and methods for antibodies targeting factor p |
WO2013093809A1 (en) | 2011-12-23 | 2013-06-27 | Pfizer Inc. | Engineered antibody constant regions for site-specific conjugation and methods and uses therefor |
WO2013100120A1 (en) | 2011-12-28 | 2013-07-04 | 中外製薬株式会社 | Humanized anti-epiregulin antibody, and cancer therapeutic agent comprising said antibody as active ingredient |
WO2013101771A2 (en) | 2011-12-30 | 2013-07-04 | Genentech, Inc. | Compositions and method for treating autoimmune diseases |
WO2013106489A1 (en) | 2012-01-09 | 2013-07-18 | The Scripps Research Institute | Humanized antibodies with ultralong cdr3s |
WO2013106485A2 (en) | 2012-01-09 | 2013-07-18 | The Scripps Research Institute | Ultralong complementarity determining regions and uses thereof |
WO2013106765A1 (en) | 2012-01-13 | 2013-07-18 | Genentech, Inc. | Biological markers for identifying patients for treatment with vegf antagonists |
WO2013112467A1 (en) | 2012-01-23 | 2013-08-01 | Trustees Of Boston University | DEspR ANTAGONISTS AND AGONISTS AS THERAPEUTICS |
EP2623516A2 (en) | 2005-12-02 | 2013-08-07 | Genentech, Inc. | Compositions and methods for the treatment of diseases and disorders associated with cytokine signaling involving antibodies that bind to IL-22 and IL-22R |
EP2626371A1 (en) | 2007-07-31 | 2013-08-14 | MedImmune, LLC | Multispecific epitope binding proteins and uses thereof |
WO2013119960A2 (en) | 2012-02-08 | 2013-08-15 | Stem Centrx, Inc. | Novel modulators and methods of use |
WO2013125667A1 (en) | 2012-02-24 | 2013-08-29 | 中外製薬株式会社 | ANTIGEN-BINDING MOLECULE FOR PROMOTING DISAPPEARANCE OF ANTIGEN VIA FcγRIIB |
US8524867B2 (en) | 2006-08-14 | 2013-09-03 | Xencor, Inc. | Optimized antibodies that target CD19 |
EP2641618A2 (en) | 2007-07-16 | 2013-09-25 | Genentech, Inc. | Humanized anti-CD79B antibodies and immunoconjugates and methods of use |
US8546539B2 (en) | 2007-05-14 | 2013-10-01 | Novimmune S.A. | Fc receptor-binding polypeptides with modified effector functions |
US8546543B2 (en) | 2004-11-12 | 2013-10-01 | Xencor, Inc. | Fc variants that extend antibody half-life |
WO2013147153A1 (en) | 2012-03-29 | 2013-10-03 | 株式会社未来創薬研究所 | Anti-lamp5 antibody and utilization thereof |
WO2013148288A1 (en) | 2012-03-30 | 2013-10-03 | Genentech, Inc. | Diagnostic methods and compositions for treatment of cancer |
WO2013148296A1 (en) | 2012-03-28 | 2013-10-03 | Sanofi | Antibodies to bradykinin b1 receptor ligands |
EP2654780A1 (en) * | 2010-12-23 | 2013-10-30 | Janssen Biotech, Inc. | Active protease-resistant antibody fc mutants |
EP2657253A2 (en) | 2008-01-31 | 2013-10-30 | Genentech, Inc. | Anti-CD79b antibodies and immunoconjugates and methods of use |
WO2013166290A1 (en) | 2012-05-04 | 2013-11-07 | Abbvie Biotherapeutics Inc. | P21 biomarker assay |
EP2662390A1 (en) | 2004-06-21 | 2013-11-13 | Medarex, L.L.C. | Interferon alpha receptor 1 antibodies and their uses |
WO2013169657A1 (en) | 2012-05-07 | 2013-11-14 | Sanofi | Methods for preventing biofilm formation |
WO2013173687A1 (en) | 2012-05-18 | 2013-11-21 | Genentech, Inc. | High-concentration monoclonal antibody formulations |
WO2013175276A1 (en) | 2012-05-23 | 2013-11-28 | Argen-X B.V | Il-6 binding molecules |
WO2013177062A2 (en) | 2012-05-21 | 2013-11-28 | Genentech, Inc. | Methods for improving safety of blood-brain barrier transport |
WO2013177386A1 (en) | 2012-05-24 | 2013-11-28 | Abbvie Biotherapeutics Inc. | Biomarkers for predicting response to tweak receptor (tweakr) agonist therapy |
WO2013174927A1 (en) | 2012-05-23 | 2013-11-28 | Novartis International Pharmaceutical Limited | Production of fucosylated glycoproteins |
WO2013180200A1 (en) | 2012-05-30 | 2013-12-05 | 中外製薬株式会社 | Target-tissue-specific antigen-binding molecule |
WO2013180201A1 (en) | 2012-05-30 | 2013-12-05 | 中外製薬株式会社 | Antigen-binding molecule for eliminating aggregated antigens |
WO2013184514A1 (en) | 2012-06-04 | 2013-12-12 | Irm Llc | Site-specific labeling methods and molecules produced thereby |
WO2013183032A2 (en) | 2012-06-08 | 2013-12-12 | Glenmark Pharmaceuticals S.A. | Anti-trka antibodies with enhanced inhibitory properties and derivatives thereof |
WO2013185113A1 (en) | 2012-06-08 | 2013-12-12 | Biogen Idec Ma Inc. | Procoagulant compounds |
WO2013185114A2 (en) | 2012-06-08 | 2013-12-12 | Biogen Idec Ma Inc. | Chimeric clotting factors |
WO2013187495A1 (en) | 2012-06-14 | 2013-12-19 | 中外製薬株式会社 | ANTIGEN-BINDING MOLECULE CONTAINING MODIFIED Fc REGION |
US8613923B2 (en) | 2007-06-12 | 2013-12-24 | Ac Immune S.A. | Monoclonal antibody |
WO2013192131A1 (en) * | 2012-06-21 | 2013-12-27 | Indiana University Research And Technology Corporation | Incretin receptor ligand polypeptide fc-region fusion polypeptides and conjugates with altered fc-effector function |
US8618248B2 (en) | 2006-10-31 | 2013-12-31 | President And Fellows Of Harvard College | Phosphopeptide compositions and anti-phosphopeptide antibody compositions and methods of detecting phosphorylated peptides |
US8618252B2 (en) | 2003-11-12 | 2013-12-31 | Biogen Idec Ma Inc. | Neonatal Fc receptor (FcRn)-binding polypeptide variants, dimeric Fc binding proteins and methods related thereto |
WO2014006217A1 (en) | 2012-07-06 | 2014-01-09 | Genmab B.V. | Dimeric protein with triple mutations |
WO2014008218A1 (en) | 2012-07-02 | 2014-01-09 | Bristol-Myers Squibb Company | Optimization of antibodies that bind lymphocyte activation gene-3 (lag-3), and uses thereof |
WO2014013019A1 (en) | 2012-07-18 | 2014-01-23 | Glycotope Gmbh | Novel therapeutic treatments with anti-her2 antibodies having a low fucosylation |
WO2014018625A1 (en) | 2012-07-25 | 2014-01-30 | Kolltan Pharmaceuticals, Inc. | Anti-kit antibodies and uses thereof |
KR20140015501A (en) | 2011-03-30 | 2014-02-06 | 추가이 세이야쿠 가부시키가이샤 | Retention of antigen-binding molecules in blood plasma and method for modifying immunogenicity |
KR101357813B1 (en) | 2004-07-12 | 2014-02-06 | 마크로제닉스, 인크. | Identification and engineering of antibodies with variant fc regions and methods of using the same |
US8647625B2 (en) | 2004-07-26 | 2014-02-11 | Biogen Idec Ma Inc. | Anti-CD154 antibodies |
WO2014030728A1 (en) | 2012-08-24 | 2014-02-27 | 中外製薬株式会社 | Fcγriib-specific fc region variant |
WO2014029752A1 (en) | 2012-08-22 | 2014-02-27 | Glaxo Group Limited | Anti lrp6 antibodies |
WO2014030750A1 (en) | 2012-08-24 | 2014-02-27 | 中外製薬株式会社 | MOUSE FcγRII-SPECIFIC Fc ANTIBODY |
EP2703011A2 (en) | 2007-05-07 | 2014-03-05 | MedImmune, LLC | Anti-icos antibodies and their use in treatment of oncology, transplantation and autoimmune disease |
WO2014033074A1 (en) | 2012-08-29 | 2014-03-06 | F. Hoffmann-La Roche Ag | Blood brain barrier shuttle |
WO2014037899A2 (en) | 2012-09-07 | 2014-03-13 | Novartis Ag | Il-18 binding molecules |
US8679492B2 (en) | 2009-02-23 | 2014-03-25 | Glenmark Pharmaceuticals S.A. | Humanized antibodies that bind to CD19 and their uses |
EP2711018A1 (en) | 2009-06-22 | 2014-03-26 | MedImmune, LLC | Engineered Fc regions for site-specific conjugation |
WO2014059028A1 (en) | 2012-10-09 | 2014-04-17 | Igenica, Inc. | Anti-c16orf54 antibodies and methods of use thereof |
WO2014072876A1 (en) | 2012-11-09 | 2014-05-15 | Pfizer Inc. | Platelet-derived growth factor b specific antibodies and compositions and uses thereof |
EP2733153A1 (en) | 2012-11-15 | 2014-05-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the preparation of immunoconjugates and uses thereof |
WO2014084859A1 (en) | 2012-11-30 | 2014-06-05 | Novartis Ag | Molecules and methods for modulating tmem16a activities |
WO2014083379A1 (en) | 2012-11-30 | 2014-06-05 | Institut Pasteur | Use of anti-fcyri and/or anti-fcyriia antibodies for treating arthritis, inflammation, thrombocytopenia and allergic shock |
WO2014089111A1 (en) | 2012-12-05 | 2014-06-12 | Novartis Ag | Compositions and methods for antibodies targeting epo |
US8753625B2 (en) | 2005-11-04 | 2014-06-17 | Genentech, Inc. | Use of complement inhibitors to treat ocular diseases |
WO2014100823A1 (en) | 2012-12-21 | 2014-06-26 | Amplimmune, Inc. | Anti-h7cr antibodies |
WO2014100483A1 (en) | 2012-12-19 | 2014-06-26 | Amplimmune, Inc. | Anti-human b7-h4 antibodies and their uses |
WO2014097648A1 (en) | 2012-12-21 | 2014-06-26 | 中外製薬株式会社 | Gpc3-targeted therapeutic agent for administration to patients for whom gpc3-targeted therapeutic agent therapy is effective |
WO2014104165A1 (en) | 2012-12-27 | 2014-07-03 | 中外製薬株式会社 | Heterodimerized polypeptide |
US8775090B2 (en) | 2008-12-12 | 2014-07-08 | Medimmune, Llc | Crystals and structure of a human IgG Fc variant with enhanced FcRn binding |
EP2752189A1 (en) | 2008-11-22 | 2014-07-09 | F. Hoffmann-La Roche AG | Use of anti-vegf antibody in combination with chemotherapy for treating breast cancer |
AU2011265460B2 (en) * | 2003-01-09 | 2014-07-17 | Macrogenics, Inc. | Identification and engineering of antibodies with variant Fc regions and methods of using same |
WO2014108198A1 (en) | 2013-01-10 | 2014-07-17 | Genmab B.V. | Human igg1 fc region variants and uses thereof |
WO2014114651A1 (en) | 2013-01-24 | 2014-07-31 | Glaxosmithkline Intellectual Property Development Limited | Tnf-alpha antigen-binding proteins |
US8796439B2 (en) | 2006-07-14 | 2014-08-05 | Ac Immune S.A. | Nucleic acid molecules encoding a humanized antibody |
US8795667B2 (en) | 2007-12-19 | 2014-08-05 | Macrogenics, Inc. | Compositions for the prevention and treatment of smallpox |
EP2762496A1 (en) | 2013-02-05 | 2014-08-06 | EngMab AG | Method for the selection of antibodies against BCMA |
US8802820B2 (en) | 2004-11-12 | 2014-08-12 | Xencor, Inc. | Fc variants with altered binding to FcRn |
WO2014122613A1 (en) | 2013-02-08 | 2014-08-14 | Novartis Ag | Anti-il-17a antibodies and their use in treating autoimmune and inflammatory disorders |
WO2014124316A2 (en) | 2013-02-08 | 2014-08-14 | Irm Llc | Specific sites for modifying antibodies to make immunoconjugates |
WO2014124258A2 (en) | 2013-02-08 | 2014-08-14 | Irm Llc | Specific sites for modifying antibodies to make immunoconjugates |
WO2014122143A1 (en) | 2013-02-05 | 2014-08-14 | Engmab Ag | Method for the selection of antibodies against bcma |
WO2014126871A1 (en) | 2013-02-12 | 2014-08-21 | Bristol-Myers Squibb Company | Tangential flow filtration based protein refolding methods |
WO2014127215A1 (en) | 2013-02-15 | 2014-08-21 | Biogen Idec Ma Inc. | Optimized factor viii gene |
WO2014125041A1 (en) | 2013-02-14 | 2014-08-21 | Innate Pharma | Treatment of peripheral t cell lymphoma |
WO2014126884A1 (en) | 2013-02-12 | 2014-08-21 | Bristol-Myers Squibb Company | High ph protein refolding methods |
EP2769993A1 (en) | 2007-12-14 | 2014-08-27 | Novo Nordisk A/S | Antibodies against human NKG2D and uses thereof |
WO2014130923A2 (en) | 2013-02-25 | 2014-08-28 | Genentech, Inc. | Methods and compositions for detecting and treating drug resistant akt mutant |
WO2014130879A2 (en) | 2013-02-22 | 2014-08-28 | Stem Centrx, Inc. | Novel antibody conjugates and uses thereof |
WO2014144911A2 (en) | 2013-03-15 | 2014-09-18 | Capon Daniel J | Hybrid immunoglobulin containing non-peptidyl linkage |
WO2014144357A1 (en) | 2013-03-15 | 2014-09-18 | Merck Patent Gmbh | Tetravalent bispecific antibodies |
WO2014145050A1 (en) | 2013-03-15 | 2014-09-18 | Atyr Pharma, Inc. | Histidyl-trna synthetase-fc conjugates |
WO2014140180A1 (en) | 2013-03-15 | 2014-09-18 | Glaxosmithkline Intellectual Property Development Limited | Anti-lag-3 binding proteins |
WO2014144791A2 (en) | 2013-03-15 | 2014-09-18 | Dana-Farber Cancer Institute, Inc. | Therapeutic peptides |
WO2014160160A2 (en) | 2013-03-13 | 2014-10-02 | Novartis Ag | Antibody drug conjugates |
WO2014159239A2 (en) | 2013-03-14 | 2014-10-02 | Novartis Ag | Antibodies against notch 3 |
US8853366B2 (en) | 2001-01-17 | 2014-10-07 | Emergent Product Development Seattle, Llc | Binding domain-immunoglobulin fusion proteins |
WO2014164503A1 (en) | 2013-03-11 | 2014-10-09 | Genzyme Corporation | Hyperglycosylated binding polypeptides |
WO2014173886A1 (en) | 2013-04-22 | 2014-10-30 | Glycotope Gmbh | Anti-cancer treatments with anti-egfr antibodies having a low fucosylation |
WO2014178820A1 (en) | 2013-04-29 | 2014-11-06 | Teva Pharmaceuticals Australia Pty Ltd. | Anti-cd38 antibodies and fusions to attenuated interferon alpha-2b |
US8883980B2 (en) | 2003-11-05 | 2014-11-11 | Roche Glycart Ag | Antigen binding molecules with increased Fc receptor binding affinity and effector function |
WO2014190356A2 (en) | 2013-05-24 | 2014-11-27 | Amplimmune, Inc. | Anti-b7-h5 antibodies and their uses |
WO2014205300A2 (en) | 2013-06-21 | 2014-12-24 | Novartis Ag | Lectin-like oxidized ldl receptor1 antibodies and methods of use |
WO2014205302A2 (en) | 2013-06-21 | 2014-12-24 | Novartis Ag | Lectin-like oxidized ldl receptor1 antibodies and methods of use |
WO2014208482A1 (en) | 2013-06-24 | 2014-12-31 | 中外製薬株式会社 | Therapeutic agent comprising humanized anti-epiregulin antibody as active ingredient for non-small-cell lung carcinoma excluding adenocarcinoma |
WO2015010100A2 (en) | 2013-07-18 | 2015-01-22 | Fabrus, Inc. | Humanized antibodies with ultralong complementarity determining regions |
EP2829551A1 (en) | 2006-10-19 | 2015-01-28 | CSL Limited | High affinity antibody antagonists of interleukin-13 receptor alpha 1 |
WO2015017146A2 (en) | 2013-07-18 | 2015-02-05 | Fabrus, Inc. | Antibodies with ultralong complementarity determining regions |
WO2015023891A2 (en) | 2013-08-14 | 2015-02-19 | Biogen Idec Ma Inc. | Factor viii-xten fusions and uses thereof |
WO2015022658A2 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Methods of treating sporadic inclusion body myositis |
WO2015023596A1 (en) | 2013-08-12 | 2015-02-19 | Genentech, Inc. | Compositions and method for treating complement-associated conditions |
US8969526B2 (en) | 2011-03-29 | 2015-03-03 | Roche Glycart Ag | Antibody Fc variants |
EP2842968A1 (en) | 2005-04-29 | 2015-03-04 | Janssen Biotech, Inc. | Anti-IL-6 antibodies, compositions, methods and uses |
WO2015031673A2 (en) | 2013-08-28 | 2015-03-05 | Bioasis Technologies Inc. | Cns-targeted conjugates having modified fc regions and methods of use thereof |
US8975376B2 (en) | 2010-02-23 | 2015-03-10 | Sanofi | Anti-alpha2 integrin antibodies and their uses |
EP2845912A1 (en) | 2006-09-12 | 2015-03-11 | Genentech, Inc. | Methods and compositions for the diagnosis and treatment of lung cancer using KIT gene as genetic marker |
EP2851372A1 (en) | 2007-11-30 | 2015-03-25 | Genentech, Inc. | Anti-VEGF antibodies |
WO2015046467A1 (en) | 2013-09-27 | 2015-04-02 | 中外製薬株式会社 | Method for producing polypeptide heteromultimer |
US9005612B2 (en) | 2001-01-17 | 2015-04-14 | Emergent Product Development Seattle, Llc | Binding domain-immunoglobulin fusion proteins |
WO2015066557A1 (en) | 2013-10-31 | 2015-05-07 | Resolve Therapeutics, Llc | Therapeutic nuclease molecules with altered glycosylation and methods |
WO2015067986A1 (en) | 2013-11-07 | 2015-05-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Neuregulin allosteric anti-her3 antibody |
WO2015068847A1 (en) | 2013-11-11 | 2015-05-14 | 中外製薬株式会社 | Antigen-binding molecule containing modified antibody variable region |
WO2015073580A1 (en) | 2013-11-13 | 2015-05-21 | Pfizer Inc. | Tumor necrosis factor-like ligand 1a specific antibodies and compositions and uses thereof |
US9051373B2 (en) | 2003-05-02 | 2015-06-09 | Xencor, Inc. | Optimized Fc variants |
WO2015083764A1 (en) | 2013-12-04 | 2015-06-11 | 中外製薬株式会社 | Antigen-binding molecules, the antigen-binding activity of which varies according to the concentration of compounds, and libraries of said molecules |
WO2015085210A1 (en) | 2013-12-06 | 2015-06-11 | Dana-Farber Cancer Institute, Inc. | Therapeutic peptides |
WO2015089117A1 (en) | 2013-12-09 | 2015-06-18 | Allakos Inc. | Anti-siglec-8 antibodies and methods of use thereof |
WO2015089375A1 (en) | 2013-12-13 | 2015-06-18 | The General Hospital Corporation | Soluble high molecular weight (hmw) tau species and applications thereof |
US9062116B2 (en) | 2009-04-23 | 2015-06-23 | Infinity Pharmaceuticals, Inc. | Anti-fatty acid amide hydrolase-2 antibodies and uses thereof |
WO2015095423A2 (en) | 2013-12-17 | 2015-06-25 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
WO2015100299A1 (en) | 2013-12-24 | 2015-07-02 | Argen-X N.V. | Fcrn antagonists and methods of use |
WO2015106052A1 (en) | 2014-01-10 | 2015-07-16 | Biogen Ma Inc. | Factor viii chimeric proteins and uses thereof |
US9085630B2 (en) | 2002-11-15 | 2015-07-21 | Genentech, Inc. | Compositions and methods for the treatment of tumor of hematopoietic origin |
WO2015109212A1 (en) | 2014-01-17 | 2015-07-23 | Pfizer Inc. | Anti-il-2 antibodies and compositions and uses thereof |
EP2899541A1 (en) | 2007-03-02 | 2015-07-29 | Genentech, Inc. | Predicting response to a HER dimerisation inhbitor based on low HER3 expression |
US9101609B2 (en) | 2008-04-11 | 2015-08-11 | Emergent Product Development Seattle, Llc | CD37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof |
EP2905030A1 (en) | 2008-08-11 | 2015-08-12 | E. R. Squibb & Sons, L.L.C. | Human antibodies that bind lymphocyte activation gene-3 (LAG-3) and uses thereof |
WO2015120075A2 (en) | 2014-02-04 | 2015-08-13 | Genentech, Inc. | Mutant smoothened and methods of using the same |
WO2015131155A1 (en) | 2014-02-28 | 2015-09-03 | Allakos Inc. | Methods and compositions for treating siglec-8 associated diseases |
US9127060B2 (en) | 2010-12-15 | 2015-09-08 | Wyeth Llc | Anti-Notch1 antibodies |
WO2015139046A1 (en) | 2014-03-14 | 2015-09-17 | Genentech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
WO2015138615A2 (en) | 2014-03-12 | 2015-09-17 | Irm Llc | Specific sites for modifying antibodies to make immunoconjugates |
WO2015143271A1 (en) | 2014-03-21 | 2015-09-24 | X-Body, Inc. | Bi-specific antigen-binding polypeptides |
US9146244B2 (en) | 2007-06-12 | 2015-09-29 | Ac Immune S.A. | Polynucleotides encoding an anti-beta-amyloid monoclonal antibody |
WO2015148809A1 (en) | 2014-03-27 | 2015-10-01 | Genentech, Inc. | Methods for diagnosing and treating inflammatory bowel disease |
EP2927244A1 (en) | 2008-09-19 | 2015-10-07 | MedImmune, LLC | Antibodies directed to DLL4 and uses thereof |
WO2015153513A1 (en) | 2014-03-31 | 2015-10-08 | Genentech, Inc. | Anti-ox40 antibodies and methods of use |
WO2015153514A1 (en) | 2014-03-31 | 2015-10-08 | Genentech, Inc. | Combination therapy comprising anti-angiogenesis agents and ox40 binding agonists |
US9156915B2 (en) | 2012-04-26 | 2015-10-13 | Thomas Jefferson University | Anti-GCC antibody molecules |
WO2015157592A1 (en) | 2014-04-11 | 2015-10-15 | Medimmune, Llc | Bispecific her2 antibodies |
WO2015162590A1 (en) | 2014-04-24 | 2015-10-29 | Novartis Ag | Methods of improving or accelerating physical recovery after surgery for hip fracture |
WO2015164330A1 (en) | 2014-04-21 | 2015-10-29 | Millennium Pharmaceuticals, Inc. | Anti-psyk antibody molecules and use of same for syk-targeted therapy |
WO2015184207A1 (en) | 2014-05-29 | 2015-12-03 | Macrogenics, Inc. | Tri-specific binding molecules that specifically bind to multiple cancer antigens and methods of use thereof |
WO2015184099A1 (en) | 2014-05-28 | 2015-12-03 | 4-Antibody Ag | Anti-gitr antibodies and methods of use thereof |
WO2015187835A2 (en) | 2014-06-06 | 2015-12-10 | Bristol-Myers Squibb Company | Antibodies against glucocorticoid-induced tumor necrosis factor receptor (gitr) and uses thereof |
US9217018B2 (en) | 2011-12-15 | 2015-12-22 | Sergei B Onikienko | HSP70 fusion protein conjugates and uses thereof |
WO2015198217A2 (en) | 2013-02-08 | 2015-12-30 | Novartis Ag | Compositions and methods for long-acting antibodies targeting il-17 |
US9234039B2 (en) | 2010-08-31 | 2016-01-12 | Sanofi | Peptide or peptide complex binding to ALPHA2 integrin and methods and uses involving the same |
EP2982379A1 (en) | 2005-07-01 | 2016-02-10 | E. R. Squibb & Sons, L.L.C. | Human monoclonal antibodies to programmed death ligand 1 (pd-l1) |
WO2016020882A2 (en) | 2014-08-07 | 2016-02-11 | Novartis Ag | Angiopoetin-like 4 (angptl4) antibodies and methods of use |
WO2016020791A1 (en) | 2014-08-05 | 2016-02-11 | Novartis Ag | Ckit antibody drug conjugates |
WO2016020880A2 (en) | 2014-08-07 | 2016-02-11 | Novartis Ag | Angiopoietin-like 4 antibodies and methods of use |
WO2016024195A1 (en) | 2014-08-12 | 2016-02-18 | Novartis Ag | Anti-cdh6 antibody drug conjugates |
WO2016028672A1 (en) | 2014-08-19 | 2016-02-25 | Merck Sharp & Dohme Corp. | Anti-lag3 antibodies and antigen-binding fragments |
WO2016028656A1 (en) | 2014-08-19 | 2016-02-25 | Merck Sharp & Dohme Corp. | Anti-tigit antibodies |
WO2016030488A1 (en) | 2014-08-27 | 2016-03-03 | Innate Pharma | Treatment of celiac disease |
US9290576B2 (en) | 2013-01-02 | 2016-03-22 | Glenmark Pharmaceuticals S.A. | Antibodies that bind to TL1A and their uses |
US9296816B2 (en) | 2005-04-15 | 2016-03-29 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
US9296815B2 (en) | 2010-03-29 | 2016-03-29 | Zymeworks Inc. | Antibodies with enhanced or suppressed effector function |
WO2016046301A1 (en) | 2014-09-26 | 2016-03-31 | Bayer Pharma Aktiengesellschaft | Stabilized adrenomedullin derivatives and use thereof |
WO2016057841A1 (en) | 2014-10-08 | 2016-04-14 | Novartis Ag | Compositions and methods of use for augmented immune response and cancer therapy |
EP3009454A2 (en) | 2009-04-20 | 2016-04-20 | Oxford Bio Therapeutics Limited | Antibodies specific to cadherin-17 |
WO2016061286A2 (en) | 2014-10-14 | 2016-04-21 | Halozyme, Inc. | Compositions of adenosine deaminase-2 (ada2), variants thereof and methods of using same |
US9321831B2 (en) | 2007-06-01 | 2016-04-26 | Medimmune Limited | RSV-specific binding molecules and means for producing them |
WO2016062851A1 (en) | 2014-10-23 | 2016-04-28 | Innate Pharma | Treatment of cancers using anti-nkg2a agents |
US9328170B2 (en) | 2011-05-25 | 2016-05-03 | Merck Sharp & Dohme Corp. | Method for preparing Fc containing polypeptides having improved properties |
WO2016073378A1 (en) | 2014-11-03 | 2016-05-12 | Genentech, Inc. | Assays for detecting t cell immune subsets and methods of use thereof |
WO2016075670A1 (en) | 2014-11-14 | 2016-05-19 | Novartis Ag | Antibody drug conjugates |
WO2016081384A1 (en) | 2014-11-17 | 2016-05-26 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
WO2016081643A1 (en) | 2014-11-19 | 2016-05-26 | Genentech, Inc. | Anti-transferrin receptor antibodies and methods of use |
WO2016081640A1 (en) | 2014-11-19 | 2016-05-26 | Genentech, Inc. | Anti-transferrin receptor / anti-bace1 multispecific antibodies and methods of use |
WO2016079597A1 (en) | 2014-11-19 | 2016-05-26 | Axon Neuroscience Se | Humanized tau antibodies in alzheimer's disease |
WO2016081748A2 (en) | 2014-11-21 | 2016-05-26 | Bristol-Myers Squibb Company | Antibodies against cd73 and uses thereof |
US9359437B2 (en) | 2013-02-01 | 2016-06-07 | Regeneron Pharmaceuticals, Inc. | Antibodies comprising chimeric constant domains |
WO2016091891A1 (en) | 2014-12-09 | 2016-06-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Human monoclonal antibodies against axl |
WO2016094566A2 (en) | 2014-12-10 | 2016-06-16 | Genentech, Inc. | Blood brain barrier receptor antibodies and methods of use |
WO2016097865A1 (en) | 2014-12-19 | 2016-06-23 | Regenesance B.V. | Antibodies that bind human c6 and uses thereof |
WO2016098079A2 (en) | 2014-12-19 | 2016-06-23 | Novartis Ag | Compositions and methods for antibodies targeting bmp6 |
US9376672B2 (en) | 2009-08-24 | 2016-06-28 | Amunix Operating Inc. | Coagulation factor IX compositions and methods of making and using same |
WO2016115345A1 (en) | 2015-01-14 | 2016-07-21 | The Brigham And Women's Hospital, | Treatment of cancer with anti-lap monoclonal antibodies |
US9403902B2 (en) | 2007-10-05 | 2016-08-02 | Ac Immune S.A. | Methods of treating ocular disease associated with amyloid-beta-related pathology using an anti-amyloid-beta antibody |
WO2016123329A2 (en) | 2015-01-28 | 2016-08-04 | Genentech, Inc. | Gene expression markers and treatment of multiple sclerosis |
WO2016126972A1 (en) | 2015-02-04 | 2016-08-11 | Genentech, Inc. | Mutant smoothened and methods of using the same |
WO2016125495A1 (en) | 2015-02-05 | 2016-08-11 | Chugai Seiyaku Kabushiki Kaisha | Antibodies comprising an ion concentration dependent antigen-binding domain, fc region variants, il-8-binding antibodies, and uses therof |
WO2016134333A1 (en) | 2015-02-19 | 2016-08-25 | Compugen Ltd. | Anti-pvrig antibodies and methods of use |
WO2016134335A2 (en) | 2015-02-19 | 2016-08-25 | Compugen Ltd. | Pvrig polypeptides and methods of treatment |
WO2016135066A1 (en) | 2015-02-26 | 2016-09-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Fusion proteins and antibodies comprising thereof for promoting apoptosis |
WO2016138207A1 (en) | 2015-02-26 | 2016-09-01 | Genentech, Inc. | Integrin beta7 antagonists and methods of treating crohn's disease |
EP3067063A1 (en) | 2008-04-02 | 2016-09-14 | MacroGenics, Inc. | Her2/neu-specific antibodies and methods of using same |
WO2016142782A1 (en) | 2015-03-09 | 2016-09-15 | Argen-X N.V. | Methods of reducing serum levels of fc-containing agents using fcrn antagonsits |
WO2016168771A2 (en) | 2015-04-17 | 2016-10-20 | Alpine Immune Sciences, Inc. | Immunomodulatory proteins with tunable affinities |
US9486507B2 (en) | 2011-06-10 | 2016-11-08 | Biogen Ma Inc. | Pro-coagulant compounds and methods of use thereof |
WO2016179517A1 (en) | 2015-05-07 | 2016-11-10 | Agenus Inc. | Anti-ox40 antibodies and methods of use thereof |
US9499634B2 (en) | 2012-06-25 | 2016-11-22 | Zymeworks Inc. | Process and methods for efficient manufacturing of highly pure asymmetric antibodies in mammalian cells |
EP3095463A2 (en) | 2008-09-16 | 2016-11-23 | F. Hoffmann-La Roche AG | Methods for treating progressive multiple sclerosis |
EP3095455A1 (en) | 2006-12-19 | 2016-11-23 | Genentech, Inc. | Vegf-specific antagonists for adjuvant and neoadjuvant therapy and the treatment of early stage tumors |
EP3095797A1 (en) | 2012-02-24 | 2016-11-23 | Stemcentrx, Inc. | Anti dll3 antibodies and methods of use thereof |
WO2016188911A1 (en) | 2015-05-22 | 2016-12-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Human monoclonal antibodies fragments inhibiting both the cath-d catalytic activity and its binding to the lrp1 receptor |
WO2016196228A1 (en) | 2015-05-29 | 2016-12-08 | Bristol-Myers Squibb Company | Antibodies against ox40 and uses thereof |
WO2016196344A1 (en) | 2015-05-30 | 2016-12-08 | Molecular Templates, Inc. | De-immunized, shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same |
WO2016196381A1 (en) | 2015-05-29 | 2016-12-08 | Genentech, Inc. | Pd-l1 promoter methylation in cancer |
WO2016193872A2 (en) | 2015-06-05 | 2016-12-08 | Novartis Ag | Antibodies targeting bone morphogenetic protein 9 (bmp9) and methods therefor |
WO2016200836A1 (en) | 2015-06-08 | 2016-12-15 | Genentech, Inc. | Methods of treating cancer using anti-ox40 antibodies |
WO2016200835A1 (en) | 2015-06-08 | 2016-12-15 | Genentech, Inc. | Methods of treating cancer using anti-ox40 antibodies and pd-1 axis binding antagonists |
WO2016203432A1 (en) | 2015-06-17 | 2016-12-22 | Novartis Ag | Antibody drug conjugates |
WO2016207858A1 (en) | 2015-06-26 | 2016-12-29 | Novartis Ag | Factor xi antibodies and methods of use |
WO2016207273A2 (en) | 2015-06-23 | 2016-12-29 | Innate Pharma | Multispecific antigen binding proteins |
WO2016207278A1 (en) | 2015-06-23 | 2016-12-29 | Innate Pharma | Multispecific nk engager proteins |
WO2017009712A1 (en) | 2015-07-13 | 2017-01-19 | Compugen Ltd. | Hide1 compositions and methods |
WO2017015619A1 (en) | 2015-07-23 | 2017-01-26 | The Regents Of The University Of California | Antibodies to coagulation factor xia and uses thereof |
WO2017019846A1 (en) | 2015-07-30 | 2017-02-02 | Macrogenics, Inc. | Pd-1-binding molecules and methods use thereof |
WO2017021893A1 (en) | 2015-08-03 | 2017-02-09 | Novartis Ag | Methods of treating fgf21-associated disorders |
WO2017023859A1 (en) | 2015-07-31 | 2017-02-09 | Memorial Sloan-Kettering Cancer Center | Antigen-binding proteins targeting cd56 and uses thereof |
EP3130349A1 (en) | 2004-06-04 | 2017-02-15 | Genentech, Inc. | Method for treating multiple sclerosis |
WO2017040790A1 (en) | 2015-09-01 | 2017-03-09 | Agenus Inc. | Anti-pd-1 antibodies and methods of use thereof |
WO2017042701A1 (en) | 2015-09-09 | 2017-03-16 | Novartis Ag | Thymic stromal lymphopoietin (tslp)-binding antibodies and methods of using the antibodies |
WO2017046746A1 (en) | 2015-09-15 | 2017-03-23 | Acerta Pharma B.V. | Therapeutic combinations of a btk inhibitor and a gitr binding molecule, a 4-1bb agonist, or an ox40 agonist |
WO2017049024A1 (en) | 2015-09-18 | 2017-03-23 | Cephalon, Inc. | Antibodies that specifically bind to tl1a |
WO2017046676A1 (en) | 2015-09-16 | 2017-03-23 | Novartis Ag | Polyomavirus neutralizing antibodies |
WO2017046994A1 (en) | 2015-09-18 | 2017-03-23 | Chugai Seiyaku Kabushiki Kaisha | Il-8-binding antibodies and uses thereof |
WO2017055542A1 (en) | 2015-10-02 | 2017-04-06 | F. Hoffmann-La Roche Ag | Bispecific anti-human cd20/human transferrin receptor antibodies and methods of use |
US9617336B2 (en) | 2012-02-01 | 2017-04-11 | Compugen Ltd | C10RF32 antibodies, and uses thereof for treatment of cancer |
WO2017062682A2 (en) | 2015-10-06 | 2017-04-13 | Genentech, Inc. | Method for treating multiple sclerosis |
WO2017066714A1 (en) | 2015-10-16 | 2017-04-20 | Compugen Ltd. | Anti-vsig1 antibodies and drug conjugates |
WO2017070561A1 (en) | 2015-10-23 | 2017-04-27 | Pfizer Inc. | Anti-il-2 antibodies and compositions and uses thereof |
US9636334B2 (en) | 2014-05-01 | 2017-05-02 | Teva Pharmaceuticals Australia Pty Ltd | Combination of lenalidomide and polypeptide construct, and uses thereof |
WO2017075229A1 (en) | 2015-10-30 | 2017-05-04 | Genentech, Inc. | Hinge modified antibody fragments and methods of making |
WO2017072662A1 (en) | 2015-10-29 | 2017-05-04 | Novartis Ag | Antibody conjugates comprising toll-like receptor agonist |
WO2017075124A1 (en) | 2015-10-29 | 2017-05-04 | Merck Sharp & Dohme Corp. | Antibody neutralizing human respiratory syncytial virus |
US9657106B2 (en) | 2003-03-03 | 2017-05-23 | Xencor, Inc. | Optimized Fc variants |
WO2017087678A2 (en) | 2015-11-19 | 2017-05-26 | Bristol-Myers Squibb Company | Antibodies against glucocorticoid-induced tumor necrosis factor receptor (gitr) and uses thereof |
WO2017096051A1 (en) | 2015-12-02 | 2017-06-08 | Stcube & Co., Inc. | Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof |
WO2017095875A1 (en) | 2015-11-30 | 2017-06-08 | Bristol-Myers Squibb Company | Anti human ip-10 antibodies and their uses |
WO2017093947A1 (en) | 2015-12-04 | 2017-06-08 | Novartis Ag | Antibody cytokine engrafted compositions and methods of use for immunoregulation |
WO2017106129A1 (en) | 2015-12-16 | 2017-06-22 | Merck Sharp & Dohme Corp. | Anti-lag3 antibodies and antigen-binding fragments |
WO2017103895A1 (en) | 2015-12-18 | 2017-06-22 | Novartis Ag | Antibodies targeting cd32b and methods of use thereof |
US9695233B2 (en) | 2012-07-13 | 2017-07-04 | Roche Glycart Ag | Bispecific anti-VEGF/anti-ANG-2 antibodies and their use in the treatment of ocular vascular diseases |
US9708408B2 (en) | 2006-12-08 | 2017-07-18 | Macrogenics, Inc. | Methods for the treatment of disease using immunoglobulins having Fc Regions with altered affinities for FcγRactivating and FcγRinhibiting |
WO2017124001A2 (en) | 2016-01-14 | 2017-07-20 | Memorial Sloan-Kettering Cancer Center | T cell receptor-like antibodies specific for foxp3-derived peptides |
US9714282B2 (en) | 2003-09-26 | 2017-07-25 | Xencor, Inc. | Optimized Fc variants and methods for their generation |
EP3199180A1 (en) | 2007-03-08 | 2017-08-02 | KaloBios Pharmaceuticals, Inc. | Epha3 antibodies for the treatment of solid tumors |
US9726673B2 (en) | 2005-11-23 | 2017-08-08 | Genentech, Inc. | Methods and compositions related to B cell assays |
WO2017136558A1 (en) | 2016-02-04 | 2017-08-10 | Curis, Inc. | Mutant smoothened and methods of using the same |
WO2017136358A1 (en) | 2016-02-01 | 2017-08-10 | Bioverativ Therapeutics Inc. | Optimized factor viii genes |
US9737599B2 (en) | 2006-06-26 | 2017-08-22 | Macrogenics, Inc. | Combination of FcγRIIB-specific antibodies and CD20-specific antibodies and methods of use thereof |
WO2017141208A1 (en) | 2016-02-17 | 2017-08-24 | Novartis Ag | Tgfbeta 2 antibodies |
EP3211094A2 (en) | 2009-09-03 | 2017-08-30 | F. Hoffmann-La Roche AG | Methods for treating, diagnosing, and monitoring rheumatoid arthritis |
WO2017152085A1 (en) | 2016-03-04 | 2017-09-08 | Bristol-Myers Squibb Company | Combination therapy with anti-cd73 antibodies |
WO2017157895A1 (en) | 2016-03-15 | 2017-09-21 | Innate Pharma | Anti-mica antibodies |
WO2017159699A1 (en) | 2016-03-15 | 2017-09-21 | Chugai Seiyaku Kabushiki Kaisha | Methods of treating cancers using pd-1 axis binding antagonists and anti-gpc3 antibodies |
WO2017161173A1 (en) | 2016-03-16 | 2017-09-21 | Merrimack Pharmaceuticals, Inc. | Engineered trail for cancer therapy |
WO2017162678A1 (en) | 2016-03-22 | 2017-09-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Humanized anti-claudin-1 antibodies and uses thereof |
WO2017172771A2 (en) | 2016-03-29 | 2017-10-05 | Janssen Biotech, Inc. | Method of treating psoriasis with increased interval dosing of anti-il12/23 antibody |
US9790268B2 (en) | 2012-09-12 | 2017-10-17 | Genzyme Corporation | Fc containing polypeptides with altered glycosylation and reduced effector function |
WO2017181139A2 (en) | 2016-04-15 | 2017-10-19 | Michael Molloy | Anti-human vista antibodies and use thereof |
WO2017181152A2 (en) | 2016-04-15 | 2017-10-19 | Alpine Immune Sciences, Inc. | Cd80 variant immunomodulatory proteins and uses thereof |
WO2017181148A2 (en) | 2016-04-15 | 2017-10-19 | Alpine Immune Sciences, Inc. | Icos ligand variant immunomodulatory proteins and uses thereof |
WO2017184562A1 (en) | 2016-04-20 | 2017-10-26 | Merck Sharp & Dohme Corp. | Cmv neutralizing antigen binding proteins |
WO2017189724A1 (en) | 2016-04-27 | 2017-11-02 | Novartis Ag | Antibodies against growth differentiation factor 15 and uses thereof |
WO2017196663A1 (en) | 2016-05-09 | 2017-11-16 | Bristol-Myers Squibb Company | Tl1a antibodies and uses thereof |
US9822181B2 (en) | 2013-08-23 | 2017-11-21 | Macrogenics, Inc. | Bi-specific monovalent diabodies that are capable of binding CD123 and CD3, and uses thereof |
US9828429B2 (en) | 2007-09-26 | 2017-11-28 | Chugai Seiyaku Kabushiki Kaisha | Method of modifying isoelectric point of antibody via amino acid substitution in CDR |
WO2017203450A1 (en) | 2016-05-25 | 2017-11-30 | Novartis Ag | Reversal binding agents for anti-factor xi/xia antibodies and uses thereof |
WO2017205721A1 (en) | 2016-05-27 | 2017-11-30 | Agenus Inc. | Anti-tim-3 antibodies and methods of use thereof |
US9845363B2 (en) | 2013-08-13 | 2017-12-19 | Sanofi | Antibodies to plasminogen activator inhibitor-1 (PAI-1) and uses thereof |
WO2017216724A1 (en) | 2016-06-15 | 2017-12-21 | Novartis Ag | Methods for treating disease using inhibitors of bone morphogenetic protein 6 (bmp6) |
WO2018005954A2 (en) | 2016-07-01 | 2018-01-04 | Resolve Therapeutics, Llc | Optimized binuclease fusions and methods |
US9868948B2 (en) | 2008-04-11 | 2018-01-16 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly |
WO2018013818A2 (en) | 2016-07-14 | 2018-01-18 | Bristol-Myers Squibb Company | Antibodies against tim3 and uses thereof |
US9879249B2 (en) | 2009-02-17 | 2018-01-30 | Redwood Bioscience, Inc. | Aldehyde-tagged protein-based drug carriers and methods of use |
WO2018020000A1 (en) | 2016-07-29 | 2018-02-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antibodies targeting tumor associated macrophages and uses thereof |
WO2018020476A1 (en) | 2016-07-29 | 2018-02-01 | Aduro Biotech Holdings, Europe B.V. | Anti-pd-1 antibodies |
WO2018022946A1 (en) | 2016-07-28 | 2018-02-01 | Alpine Immune Sciences, Inc. | Cd155 variant immunomodulatory proteins and uses thereof |
WO2018022945A1 (en) | 2016-07-28 | 2018-02-01 | Alpine Immune Sciences, Inc. | Cd112 variant immunomodulatory proteins and uses thereof |
EP3279215A1 (en) | 2009-11-24 | 2018-02-07 | MedImmune Limited | Targeted binding agents against b7-h1 |
WO2018027203A1 (en) | 2016-08-05 | 2018-02-08 | Allakos, Inc. | Anti-siglec-7 antibodies for the treatment of cancer |
WO2018025178A1 (en) | 2016-08-02 | 2018-02-08 | Aduro Biotech Holdings, Europe B.V. | Antibodies against human ctla-4 |
US9896508B2 (en) | 2010-03-04 | 2018-02-20 | Macrogenics, Inc. | Antibodies reactive with B7-H3 and uses thereof |
WO2018033798A1 (en) | 2016-08-17 | 2018-02-22 | Compugen Ltd. | Anti-tigit antibodies, anti-pvrig antibodies and combinations thereof |
US9908938B2 (en) | 2013-03-14 | 2018-03-06 | Macrogenics, Inc. | Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor and an antigen expressed by a cell infected by a virus and uses thereof |
WO2018044970A1 (en) | 2016-08-31 | 2018-03-08 | University Of Rochester | Human monoclonal antibodies to human endogenous retrovirus k envelope (herv-k) and uses thereof |
WO2018045379A1 (en) | 2016-09-02 | 2018-03-08 | Dana-Farber Cancer Institute, Inc. | Composition and methods of treating b cell disorders |
US9914785B2 (en) | 2012-11-28 | 2018-03-13 | Zymeworks Inc. | Engineered immunoglobulin heavy chain-light chain pairs and uses thereof |
WO2018053032A1 (en) | 2016-09-13 | 2018-03-22 | Humanigen, Inc. | Epha3 antibodies for the treatment of pulmonary fibrosis |
WO2018052818A1 (en) | 2016-09-16 | 2018-03-22 | Henlix, Inc. | Anti-pd-1 antibodies |
WO2018058022A1 (en) | 2016-09-26 | 2018-03-29 | Merck Sharp & Dohme Corp. | Anti-cd27 antibodies |
WO2018057735A1 (en) | 2016-09-21 | 2018-03-29 | Nextcure, Inc. | Antibodies for siglec-15 and methods of use thereof |
US9932400B2 (en) | 2013-08-23 | 2018-04-03 | Macrogenics, Inc. | Bi-specific monovalent diabodies that are capable of binding to gpA33 and CD3, and uses thereof |
WO2018064436A1 (en) | 2016-09-30 | 2018-04-05 | Janssen Biotech, Inc. | Safe and effective method of treating psoriasis with anti-il23 specific antibody |
WO2018071500A1 (en) | 2016-10-11 | 2018-04-19 | Agenus Inc. | Anti-lag-3 antibodies and methods of use thereof |
WO2018073363A1 (en) | 2016-10-21 | 2018-04-26 | Innate Pharma | Treatment with anti-kir3dl2 agents |
US9963510B2 (en) | 2005-04-15 | 2018-05-08 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
WO2018083204A1 (en) | 2016-11-02 | 2018-05-11 | Engmab Sàrl | Bispecific antibody against bcma and cd3 and an immunological drug for combined use in treating multiple myeloma |
WO2018087720A1 (en) | 2016-11-14 | 2018-05-17 | Novartis Ag | Compositions, methods, and therapeutic uses related to fusogenic protein minion |
WO2018093841A1 (en) | 2016-11-16 | 2018-05-24 | Janssen Biotech, Inc. | Method of treating psoriasis with anti-il-23 specific antibody |
EP3327035A1 (en) | 2010-06-22 | 2018-05-30 | Precision Biologics Inc. | Colon and pancreas cancer specific antigens and antibodies |
WO2018098363A2 (en) | 2016-11-23 | 2018-05-31 | Bioverativ Therapeutics Inc. | Bispecific antibodies binding to coagulation factor ix and coagulation factor x |
WO2018102760A1 (en) | 2016-12-02 | 2018-06-07 | Bioverativ Therapeutics Inc. | Methods of inducing immune tolerance to clotting factors |
WO2018102743A1 (en) | 2016-12-02 | 2018-06-07 | Bioverativ Therapeutics Inc. | Methods of treating hemophilic arthropathy using chimeric clotting factors |
US9993550B2 (en) | 1999-05-07 | 2018-06-12 | Genentech, Inc. | Treatment of pemphigus |
WO2018106862A1 (en) | 2016-12-07 | 2018-06-14 | Agenus Inc. | Anti-ctla-4 antibodies and methods of use thereof |
WO2018104893A1 (en) | 2016-12-06 | 2018-06-14 | Glaxosmithkline Intellectual Property Development Limited | Alpha4-beta7 antibodies with incrased fcrn binding and/or half-life |
WO2018106864A1 (en) | 2016-12-07 | 2018-06-14 | Agenus Inc. | Antibodies and methods of use thereof |
US10000560B2 (en) | 2014-12-19 | 2018-06-19 | Chugai Seiyaku Kabushiki Kaisha | Anti-myostatin antibodies, polypeptides containing variant Fc regions, and methods of use |
EP3336104A1 (en) | 2012-12-28 | 2018-06-20 | Precision Biologics, Inc. | Humanized monoclonal antibodies and methods of use for the diagnosis and treatment of colon and pancreas cancer |
EP3338793A1 (en) | 2013-08-28 | 2018-06-27 | AbbVie Stemcentrx LLC | Novel sez6 modulators and methods of use |
WO2018115262A1 (en) | 2016-12-23 | 2018-06-28 | Innate Pharma | Heterodimeric antigen binding proteins |
WO2018116255A1 (en) | 2016-12-23 | 2018-06-28 | Novartis Ag | Factor xi antibodies and methods of use |
US10011658B2 (en) | 2015-04-03 | 2018-07-03 | Eureka Therapeutics, Inc. | Constructs targeting AFP peptide/MHC complexes and uses thereof |
WO2018129332A1 (en) | 2017-01-06 | 2018-07-12 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes (tils) with tumor necrosis factor receptor superfamily (tnfrsf) agonists and therapeutic combinations of tils and tnfrsf agonists |
WO2018129029A1 (en) | 2017-01-04 | 2018-07-12 | Immunogen, Inc. | Met antibodies and immunoconjugates and uses thereof |
WO2018129336A1 (en) | 2017-01-06 | 2018-07-12 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes with potassium channel agonists and therapeutic uses thereof |
US10023628B2 (en) | 2012-07-06 | 2018-07-17 | Bioverativ Therapeutics Inc. | Cell line expressing single chain factor VIII polypeptides and uses thereof |
US10035843B2 (en) | 2009-10-06 | 2018-07-31 | Medimmune Limited | RSV-specific binding molecule |
EP3360567A1 (en) | 2007-11-07 | 2018-08-15 | Genentech, Inc. | Amp for use in treating microbial disorders |
WO2018146594A1 (en) | 2017-02-08 | 2018-08-16 | Novartis Ag | Fgf21 mimetic antibodies and uses thereof |
US10053511B2 (en) | 2013-11-06 | 2018-08-21 | Abbvie Stemcentrx Llc | Anti-claudin antibodies and methods of use |
US10053510B2 (en) | 2013-05-24 | 2018-08-21 | Promis Neurosciences Inc. | FasR antibodies and methods of use |
WO2018151821A1 (en) | 2017-02-17 | 2018-08-23 | Bristol-Myers Squibb Company | Antibodies to alpha-synuclein and uses thereof |
US10064952B2 (en) | 2014-10-09 | 2018-09-04 | Genzyme Corporation | Glycoengineered antibody drug conjugates |
WO2018158398A1 (en) | 2017-03-02 | 2018-09-07 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antibodies having specificity to nectin-4 and uses thereof |
WO2018160536A1 (en) | 2017-02-28 | 2018-09-07 | Bristol-Myers Squibb Company | Use of anti-ctla-4 antibodies with enhanced adcc to enhance immune response to a vaccine |
EP2647707B1 (en) | 2010-11-30 | 2018-09-12 | Chugai Seiyaku Kabushiki Kaisha | Cytotoxicity-inducing therapeutic agent |
WO2018170023A1 (en) | 2017-03-16 | 2018-09-20 | Alpine Immune Sciences, Inc. | Pd-l2 variant immunomodulatory proteins and uses thereof |
WO2018170026A2 (en) | 2017-03-16 | 2018-09-20 | Alpine Immune Sciences, Inc. | Cd80 variant immunomodulatory proteins and uses thereof |
WO2018170021A1 (en) | 2017-03-16 | 2018-09-20 | Alpine Immune Sciences, Inc. | Pd-l1 variant immunomodulatory proteins and uses thereof |
WO2018175460A1 (en) | 2017-03-24 | 2018-09-27 | Novartis Ag | Methods for preventing and treating heart disease |
US10093738B2 (en) | 2005-04-15 | 2018-10-09 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
WO2018187518A1 (en) | 2017-04-07 | 2018-10-11 | Merck Sharp & Dohme Corp. | Anti-ilt4 antibodies and antigen-binding fragments |
WO2018185618A1 (en) | 2017-04-03 | 2018-10-11 | Novartis Ag | Anti-cdh6 antibody drug conjugates and anti-gitr antibody combinations and methods of treatment |
US10100115B2 (en) | 2014-02-14 | 2018-10-16 | Macrogenics, Inc. | Methods for the treatment of vascularizing cancers |
WO2018191502A2 (en) | 2017-04-13 | 2018-10-18 | Agenus Inc. | Anti-cd137 antibodies and methods of use thereof |
WO2018189379A1 (en) | 2017-04-14 | 2018-10-18 | Gamamabs Pharma | Amhrii-binding compounds for preventing or treating cancers |
WO2018189381A1 (en) | 2017-04-14 | 2018-10-18 | Gamamabs Pharma | Amhrii-binding compounds for preventing or treating lung cancers |
WO2018195338A1 (en) | 2017-04-20 | 2018-10-25 | Atyr Pharma, Inc. | Compositions and methods for treating lung inflammation |
WO2018198091A1 (en) | 2017-04-28 | 2018-11-01 | Novartis Ag | Antibody conjugates comprising toll-like receptor agonist and combination therapies |
WO2018204363A1 (en) | 2017-05-01 | 2018-11-08 | Agenus Inc. | Anti-tigit antibodies and methods of use thereof |
EP3401335A1 (en) | 2008-01-30 | 2018-11-14 | Genentech, Inc. | Composition comprising antibody that binds to domain ii of her2 and acidic variants thereof |
WO2018209115A1 (en) | 2017-05-10 | 2018-11-15 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof |
WO2018213097A1 (en) | 2017-05-15 | 2018-11-22 | University Of Rochester | Broadly neutralizing anti-influenza monoclonal antibody and uses thereof |
US10138291B2 (en) | 2012-07-11 | 2018-11-27 | Bioverativ Therapeutics Inc. | Factor VIII complex with XTEN and von Willebrand Factor protein, and uses thereof |
WO2018215937A1 (en) | 2017-05-24 | 2018-11-29 | Novartis Ag | Interleukin-7 antibody cytokine engrafted proteins and methods of use in the treatment of cancer |
WO2018215936A1 (en) | 2017-05-24 | 2018-11-29 | Novartis Ag | Antibody-cytokine engrafted proteins and methods of use in the treatment of cancer |
WO2018215935A1 (en) | 2017-05-24 | 2018-11-29 | Novartis Ag | Antibody-cytokine engrafted proteins and methods of use for immune related disorders |
WO2018215938A1 (en) | 2017-05-24 | 2018-11-29 | Novartis Ag | Antibody-cytokine engrafted proteins and methods of use |
WO2018218056A1 (en) | 2017-05-25 | 2018-11-29 | Birstol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
WO2018222685A1 (en) | 2017-05-31 | 2018-12-06 | Stcube & Co., Inc. | Methods of treating cancer using antibodies and molecules that immunospecifically bind to btn1a1 |
WO2018222689A1 (en) | 2017-05-31 | 2018-12-06 | Stcube & Co., Inc. | Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof |
WO2018220446A1 (en) | 2017-06-01 | 2018-12-06 | Compugen Ltd. | Triple combination antibody therapies |
EP3412309A1 (en) | 2011-03-31 | 2018-12-12 | F. Hoffmann-La Roche AG | Methods of administering beta7 integrin antagonists |
WO2018226671A1 (en) | 2017-06-06 | 2018-12-13 | Stcube & Co., Inc. | Methods of treating cancer using antibodies and molecules that bind to btn1a1 or btn1a1-ligands |
WO2018229706A1 (en) | 2017-06-16 | 2018-12-20 | Novartis Ag | Combination therapy for the treatment of cancer |
WO2018229612A1 (en) | 2017-06-12 | 2018-12-20 | Novartis Ag | Method of manufacturing bispecific antibodies, bispecific antibodies and therapeutic use of such antibodies |
WO2018229715A1 (en) | 2017-06-16 | 2018-12-20 | Novartis Ag | Compositions comprising anti-cd32b antibodies and methods of use thereof |
WO2019003104A1 (en) | 2017-06-28 | 2019-01-03 | Novartis Ag | Methods for preventing and treating urinary incontinence |
EP3424530A1 (en) | 2013-03-15 | 2019-01-09 | Zyngenia, Inc. | Multivalent and monovalent multispecific complexes and their uses |
US10179821B2 (en) | 2014-05-01 | 2019-01-15 | Genentech, Inc. | Anti-factor D antibodies |
US10183998B2 (en) | 2011-01-14 | 2019-01-22 | Redwood Bioscience, Inc. | Aldehyde-tagged immunoglobulin polypeptides and methods of use thereof |
KR20190009272A (en) | 2016-06-17 | 2019-01-28 | 추가이 세이야쿠 가부시키가이샤 | Anti-myostatin antibodies and methods of use |
WO2019032898A1 (en) | 2017-08-09 | 2019-02-14 | Bioverativ Therapeutics Inc. | Nucleic acid molecules and uses thereof |
US10208120B2 (en) | 2014-11-05 | 2019-02-19 | Genentech, Inc. | Anti-FGFR2/3 antibodies and methods using same |
WO2019040674A1 (en) | 2017-08-22 | 2019-02-28 | Sanabio, Llc | Soluble interferon receptors and uses thereof |
WO2019040780A1 (en) | 2017-08-25 | 2019-02-28 | Five Prime Therapeutics Inc. | B7-h4 antibodies and methods of use thereof |
EP3456736A1 (en) | 2017-09-19 | 2019-03-20 | Tillotts Pharma Ag | Antibody variants |
EP3456737A1 (en) | 2017-09-19 | 2019-03-20 | Tillotts Pharma Ag | Antibody variants |
US10239946B2 (en) | 2015-03-31 | 2019-03-26 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Cell line overexpressing human CD303 antigen |
WO2019058345A2 (en) | 2017-09-25 | 2019-03-28 | Janssen Biotech, Inc. | Safe and effective method of treating lupus with anti-il12/il23 antibody |
WO2019059411A1 (en) | 2017-09-20 | 2019-03-28 | Chugai Seiyaku Kabushiki Kaisha | Dosage regimen for combination therapy using pd-1 axis binding antagonists and gpc3 targeting agent |
US10251952B2 (en) | 2014-06-26 | 2019-04-09 | Hoffmann-La Roche Inc. | Humanized anti-tau(pS422) antibody brain shuttles and use thereof |
WO2019074983A1 (en) | 2017-10-10 | 2019-04-18 | Alpine Immune Sciences, Inc. | Ctla-4 variant immunomodulatory proteins and uses thereof |
WO2019075090A1 (en) | 2017-10-10 | 2019-04-18 | Tilos Therapeutics, Inc. | Anti-lap antibodies and uses thereof |
WO2019079520A2 (en) | 2017-10-18 | 2019-04-25 | Alpine Immune Sciences, Inc. | Variant icos ligand immunomodulatory proteins and related compositions and methods |
WO2019081983A1 (en) | 2017-10-25 | 2019-05-02 | Novartis Ag | Antibodies targeting cd32b and methods of use thereof |
US10279021B2 (en) | 2014-03-14 | 2019-05-07 | Dana-Faber Cancer Institute, Inc. | Vaccine compositions and methods for restoring NKG2D pathway function against cancers |
WO2019093342A1 (en) | 2017-11-08 | 2019-05-16 | 協和発酵キリン株式会社 | BISPECIFIC ANTIBODY WHICH BINDS TO CD40 AND EpCAM |
WO2019103857A1 (en) | 2017-11-22 | 2019-05-31 | Iovance Biotherapeutics, Inc. | Expansion of peripheral blood lymphocytes (pbls) from peripheral blood |
WO2019101695A1 (en) | 2017-11-21 | 2019-05-31 | Innate Pharma | Multispecific antigen binding proteins |
WO2019102353A1 (en) | 2017-11-22 | 2019-05-31 | Novartis Ag | Reversal binding agents for anti-factor xi/xia antibodies and uses thereof |
WO2019106578A2 (en) | 2017-12-01 | 2019-06-06 | Novartis Ag | Polyomavirus neutralizing antibodies |
EP3495814A2 (en) | 2013-03-27 | 2019-06-12 | F. Hoffmann-La Roche AG | Use of biomarkers for assessing treatment of gastrointestinal inflammatory disorders with beta7 integrin antagonists |
WO2019110823A1 (en) | 2017-12-08 | 2019-06-13 | Argenx Bvba | Use of fcrn antagonists for treatment of generalized myasthenia gravis |
EP3498293A1 (en) | 2017-12-15 | 2019-06-19 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Treatment of monogenic diseases with an anti-cd45rc antibody |
WO2019118873A2 (en) | 2017-12-15 | 2019-06-20 | Iovance Biotherapeutics, Inc. | Systems and methods for determining the beneficial administration of tumor infiltrating lymphocytes, and methods of use thereof and beneficial administration of tumor infiltrating lymphocytes, and methods of use thereof |
WO2019126133A1 (en) | 2017-12-20 | 2019-06-27 | Alexion Pharmaceuticals, Inc. | Liquid formulations of anti-cd200 antibodies |
WO2019126536A1 (en) | 2017-12-20 | 2019-06-27 | Alexion Pharmaceuticals Inc. | Humanized anti-cd200 antibodies and uses thereof |
EP3505179A1 (en) | 2012-01-12 | 2019-07-03 | Bioverativ Therapeutics Inc. | Chimeric factor viii polypeptides and uses thereof |
WO2019129848A1 (en) | 2017-12-29 | 2019-07-04 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Method for purifying antibodies from raw milk |
JP2019518712A (en) * | 2016-03-14 | 2019-07-04 | ウニヴァーシテテット イ オスロ | Modified immunoglobulin with altered FcRn |
US10344092B2 (en) | 2013-08-09 | 2019-07-09 | Macrogenics, Inc. | Bi-specific monovalent Fc diabodies that are capable of binding CD32B and CD79b and uses thereof |
WO2019136179A1 (en) | 2018-01-03 | 2019-07-11 | Alpine Immune Sciences, Inc. | Multi-domain immunomodulatory proteins and methods of use thereof |
WO2019140229A1 (en) | 2018-01-12 | 2019-07-18 | Bristol-Myers Squibb Company | Antibodies against tim3 and uses thereof |
US10358500B2 (en) | 2014-04-04 | 2019-07-23 | Bionomics Inc. | Humanized antibodies that bind LGR5 |
EP3514178A1 (en) | 2013-03-15 | 2019-07-24 | Novartis AG | Antibody drug conjugates |
US10363496B2 (en) | 2014-09-05 | 2019-07-30 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Method for purification of monoclonal antibodies |
WO2019147973A1 (en) * | 2018-01-26 | 2019-08-01 | Genzyme Corporation | Fc variants with enhanced binding to fcrn and prolonged half-life |
US10370455B2 (en) | 2014-12-05 | 2019-08-06 | Immunext, Inc. | Identification of VSIG8 as the putative VISTA receptor (V-R) and use thereof to produce VISTA/VSIG8 agonists and antagonists |
US10370430B2 (en) | 2012-02-15 | 2019-08-06 | Bioverativ Therapeutics Inc. | Recombinant factor VIII proteins |
EP3521312A1 (en) | 2013-02-20 | 2019-08-07 | Innate Pharma, S.A. | A compound that specifically binds to kir3dl2 for use in the treatment of peripheral t cell lymphoma |
EP3520816A2 (en) | 2009-10-23 | 2019-08-07 | Millennium Pharmaceuticals, Inc. | Anti-gcc antibody molecules and related compositions and methods |
WO2019152642A1 (en) | 2018-02-01 | 2019-08-08 | Merck Sharp & Dohme Corp. | Anti-pd-1/lag3 bispecific antibodies |
WO2019152692A1 (en) | 2018-02-01 | 2019-08-08 | Bioverativ Therapeutics, Inc. | Use of lentiviral vectors expressing factor viii |
WO2019160829A1 (en) | 2018-02-13 | 2019-08-22 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes (tils) with adenosine a2a receptor antagonists and therapeutic combinations of tils and adenosine a2a receptor antagonists |
WO2019169229A1 (en) | 2018-03-01 | 2019-09-06 | Nextcure, Inc. | Klrg1 binding compositions and methods of use thereof |
WO2019168403A2 (en) | 2018-03-02 | 2019-09-06 | Labo Bio-Medical Investments B.V. | Multispecific binding molecules for the prevention, treatment and diagnosis of neurodegenerative disorders |
US10407510B2 (en) | 2015-10-30 | 2019-09-10 | Genentech, Inc. | Anti-factor D antibodies and conjugates |
WO2019171252A1 (en) | 2018-03-05 | 2019-09-12 | Janssen Biotech, Inc. | Methods of treating crohn's disease with anti-il23 specific antibody |
US10415015B2 (en) | 2016-10-31 | 2019-09-17 | Iovance Biotherapeutics, Inc. | Engineered artificial antigen presenting cells for tumor infiltrating lymphocyte expansion |
US10421798B2 (en) | 2012-02-15 | 2019-09-24 | Bioverativ Therapeutics Inc. | Factor VIII compositions and methods of making and using same |
WO2019183040A1 (en) | 2018-03-21 | 2019-09-26 | Five Prime Therapeutics, Inc. | ANTIBODIES BINDING TO VISTA AT ACIDIC pH |
US10428156B2 (en) | 2014-09-05 | 2019-10-01 | Abbvie Stemcentrx Llc | Anti-MFI2 antibodies and methods of use |
US10428145B2 (en) | 2015-09-29 | 2019-10-01 | Celgene Corporation | PD-1 binding proteins and methods of use thereof |
WO2019191295A1 (en) | 2018-03-28 | 2019-10-03 | Bristol-Myers Squibb Company | Interleukin-2/interleukin-2 receptor alpha fusion proteins and methods of use |
WO2019195126A1 (en) | 2018-04-02 | 2019-10-10 | Bristol-Myers Squibb Company | Anti-trem-1 antibodies and uses thereof |
EP3552631A1 (en) | 2018-04-10 | 2019-10-16 | Inatherys | Antibody-drug conjugates and their uses for the treatment of cancer |
US10450379B2 (en) | 2005-11-15 | 2019-10-22 | Genetech, Inc. | Method for treating joint damage |
EP3557260A1 (en) | 2012-12-21 | 2019-10-23 | Chugai Seiyaku Kabushiki Kaisha | Gpc3-targeting drug which is administered to patient responsive to gpc3-targeting drug therapy |
US10465000B2 (en) | 2013-12-20 | 2019-11-05 | Hoffmann-La Roche Inc. | Humanized anti-Tau(pS422) antibodies and methods of use |
WO2019213384A1 (en) | 2018-05-03 | 2019-11-07 | University Of Rochester | Anti-influenza neuraminidase monoclonal antibodies and uses thereof |
WO2019215701A1 (en) | 2018-05-11 | 2019-11-14 | Janssen Biotech, Inc. | Methods of treating depression using il-23 antibodies |
WO2019218009A1 (en) | 2018-05-16 | 2019-11-21 | Csl Limited | Soluble complement receptor type 1 variants and uses thereof |
WO2019222682A1 (en) | 2018-05-18 | 2019-11-21 | Bioverativ Therapeutics Inc. | Methods of treating hemophilia a |
EP3572431A1 (en) | 2014-03-14 | 2019-11-27 | Innate Pharma | Humanized antibodies with stability |
WO2019232484A1 (en) | 2018-06-01 | 2019-12-05 | Compugen Ltd | Anti-pvrig/anti-tigit bispecific antibodies and methods of use |
WO2019229699A1 (en) | 2018-05-31 | 2019-12-05 | Novartis Ag | Hepatitis b antibodies |
WO2019229701A2 (en) | 2018-06-01 | 2019-12-05 | Novartis Ag | Binding molecules against bcma and uses thereof |
WO2019229658A1 (en) | 2018-05-30 | 2019-12-05 | Novartis Ag | Entpd2 antibodies, combination therapies, and methods of using the antibodies and combination therapies |
US10501552B2 (en) | 2015-01-26 | 2019-12-10 | Macrogenics, Inc. | Multivalent molecules comprising DR5-binding domains |
WO2019236417A1 (en) | 2018-06-04 | 2019-12-12 | Biogen Ma Inc. | Anti-vla-4 antibodies having reduced effector function |
WO2019235426A1 (en) | 2018-06-04 | 2019-12-12 | 中外製薬株式会社 | Antigen-binding molecule showing changed half-life in cytoplasm |
WO2019241758A1 (en) | 2018-06-15 | 2019-12-19 | Alpine Immune Sciences, Inc. | Pd-1 variant immunomodulatory proteins and uses thereof |
US10519234B2 (en) | 2014-06-27 | 2019-12-31 | Innate Pharma | NKp46 binding proteins |
WO2020010117A2 (en) | 2018-07-03 | 2020-01-09 | Bristol-Myers Squibb Company | Fgf21 formulations |
EP3594240A1 (en) | 2013-05-20 | 2020-01-15 | F. Hoffmann-La Roche AG | Anti-transferrin receptor antibodies and methods of use |
WO2020014306A1 (en) | 2018-07-10 | 2020-01-16 | Immunogen, Inc. | Met antibodies and immunoconjugates and uses thereof |
WO2020014327A2 (en) | 2018-07-11 | 2020-01-16 | Five Prime Therapeutics, Inc. | Antibodies binding to vista at acidic ph |
WO2020014132A2 (en) | 2018-07-09 | 2020-01-16 | Five Prime Therapeutics, Inc. | Antibodies binding to ilt4 |
WO2020016838A2 (en) | 2018-07-18 | 2020-01-23 | Janssen Biotech, Inc. | Sustained response predictors after treatment with anti-il23 specific antibody |
US10544199B2 (en) | 2014-10-29 | 2020-01-28 | Teva Pharmaceuticals Australia Pty Ltd | Interferon alpha 2B variants |
US10550193B2 (en) | 2014-03-19 | 2020-02-04 | Regeneron Pharmaceuticals, Inc. | Methods and antibody compositions for tumor treatment |
US10556952B2 (en) | 2015-03-30 | 2020-02-11 | Regeneron Pharmaceuticals, Inc. | Heavy chain constant regions with reduced binding to Fc gamma receptors |
WO2020033863A1 (en) | 2018-08-09 | 2020-02-13 | Bioverativ Therapeutics Inc. | Nucleic acid molecules and uses thereof for non-viral gene therapy |
EP3613433A1 (en) | 2014-05-30 | 2020-02-26 | Henlix Biotech Co., Ltd. | Anti-epidermal growth factor receptor (egfr) antibodies |
US10584147B2 (en) | 2013-11-08 | 2020-03-10 | Biovertiv Therapeutics Inc. | Procoagulant fusion compound |
EP3620472A1 (en) | 2013-08-13 | 2020-03-11 | Sanofi | Antibodies to plasminogen activator inhibitor-1 (pai-1) and uses thereof |
WO2020056077A1 (en) | 2018-09-13 | 2020-03-19 | The Board Of Regents Of The University Of Texas System | Novel lilrb4 antibodies and uses thereof |
WO2020053742A2 (en) | 2018-09-10 | 2020-03-19 | Novartis Ag | Anti-hla-hbv peptide antibodies |
WO2020061210A1 (en) | 2018-09-18 | 2020-03-26 | Merrimack Pharmaceuticals, Inc. | Anti-tnfr2 antibodies and uses thereof |
WO2020061376A2 (en) | 2018-09-19 | 2020-03-26 | Alpine Immune Sciences, Inc. | Methods and uses of variant cd80 fusion proteins and related constructs |
US10604577B2 (en) | 2015-10-22 | 2020-03-31 | Allakos Inc. | Methods and compositions for treating systemic mastocytosis |
US10604561B2 (en) | 2016-09-16 | 2020-03-31 | Chugai Seiyaku Kabushiki Kaisha | Anti-dengue virus antibodies, polypeptides containing variant Fc regions, and methods of use |
WO2020065532A1 (en) | 2018-09-24 | 2020-04-02 | Janssen Biotech, Inc. | Safe and effective method of treating ulcerative colitis with anti-il12/il23 antibody |
US10611794B2 (en) | 2013-09-25 | 2020-04-07 | Bioverativ Therapeutics Inc. | On-column viral inactivation methods |
EP3633371A1 (en) | 2014-12-18 | 2020-04-08 | F. Hoffmann-La Roche AG | Assay and method for determining cdc eliciting antibodies |
EP3632462A1 (en) | 2012-07-06 | 2020-04-08 | Genmab B.V. | Dimeric protein with triple mutations |
WO2020076969A2 (en) | 2018-10-10 | 2020-04-16 | Tilos Therapeutics, Inc. | Anti-lap antibody variants and uses thereof |
WO2020079580A1 (en) | 2018-10-15 | 2020-04-23 | Novartis Ag | Trem2 stabilizing antibodies |
US10640564B2 (en) | 2014-10-17 | 2020-05-05 | Ichnos Sciences SA | Antibodies that bind to CCR6 and their uses |
WO2020089811A1 (en) | 2018-10-31 | 2020-05-07 | Novartis Ag | Dc-sign antibody drug conjugates |
WO2020089437A1 (en) | 2018-10-31 | 2020-05-07 | Engmab Sàrl | Combination therapy |
WO2020096989A1 (en) | 2018-11-05 | 2020-05-14 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients refractory for anti-pd-1 antibody |
WO2020096682A2 (en) | 2018-08-31 | 2020-05-14 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients refractory for anti-pd-1 antibody |
US10654932B2 (en) | 2015-10-30 | 2020-05-19 | Genentech, Inc. | Anti-factor D antibody variant conjugates and uses thereof |
US10653791B2 (en) | 2014-11-21 | 2020-05-19 | Bristol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
EP3653641A1 (en) | 2004-02-19 | 2020-05-20 | Genentech, Inc. | Cdr-repaired antibodies |
WO2020102555A1 (en) | 2018-11-16 | 2020-05-22 | Memorial Sloan Kettering Cancer Center | Antibodies to mucin-16 and methods of use thereof |
US10662244B2 (en) | 2014-11-17 | 2020-05-26 | Regeneron Pharmaceuticals, Inc. | Methods for tumor treatment using CD3XCD20 bispecific antibody |
WO2020104705A2 (en) | 2018-11-23 | 2020-05-28 | Katholieke Universiteit Leuven | Predicting a treatment response in inflammatory bowel disease |
WO2020104943A2 (en) | 2018-11-20 | 2020-05-28 | Janssen Biotech, Inc. | Safe and effective method of treating psoriasis with anti-il-23 specific antibody |
WO2020112781A1 (en) | 2018-11-28 | 2020-06-04 | Bristol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
WO2020113141A2 (en) | 2018-11-30 | 2020-06-04 | Alpine Immune Sciences, Inc. | Cd86 variant immunomodulatory proteins and uses thereof |
WO2020115115A1 (en) | 2018-12-05 | 2020-06-11 | Morphosys Ag | Multispecific antigen-binding molecules |
WO2020118011A1 (en) | 2018-12-06 | 2020-06-11 | Alexion Pharmaceuticals, Inc. | Anti-alk2 antibodies and uses thereof |
WO2020116560A1 (en) | 2018-12-05 | 2020-06-11 | 株式会社バイカ・セラピュティクス | Modified product of fc domain of antibody |
US10689447B2 (en) | 2011-02-04 | 2020-06-23 | Genentech, Inc. | Fc variants and methods for their production |
EP3670535A1 (en) | 2015-08-03 | 2020-06-24 | EngMab Sàrl | Monoclonal antibodies against bcma |
WO2020132230A2 (en) | 2018-12-20 | 2020-06-25 | Genentech, Inc. | Modified antibody fcs and methods of use |
WO2020127509A1 (en) | 2018-12-18 | 2020-06-25 | Catapult Therapeutics B.V. | The use of anti-ccr7 mabs for the prevention or treatment of graft-versus-host disease (gvhd) |
WO2020128864A1 (en) | 2018-12-18 | 2020-06-25 | Janssen Biotech, Inc. | Safe and effective method of treating lupus with anti-il12/il23 antibody |
WO2020128863A1 (en) | 2018-12-19 | 2020-06-25 | Novartis Ag | Anti-tnf-alpha antibodies |
WO2020138487A1 (en) | 2018-12-28 | 2020-07-02 | 協和キリン株式会社 | BISPECIFIC ANTIBODY BINDING TO TfR |
WO2020139926A2 (en) | 2018-12-26 | 2020-07-02 | Akrevia Therapeutics Inc. | Anti-ctla4 antibodies and methods of use thereof |
WO2020142740A1 (en) | 2019-01-04 | 2020-07-09 | Resolve Therapeutics, Llc | Treatment of sjogren's disease with nuclease fusion proteins |
US10717778B2 (en) | 2014-09-29 | 2020-07-21 | Duke University | Bispecific molecules comprising an HIV-1 envelope targeting arm |
WO2020148207A1 (en) | 2019-01-14 | 2020-07-23 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Human monoclonal antibodies binding to hla-a2 |
WO2020154405A2 (en) | 2019-01-22 | 2020-07-30 | Genentech, Inc. | Immunoglobulin a antibodies and methods of production and use |
WO2020153467A1 (en) | 2019-01-24 | 2020-07-30 | 中外製薬株式会社 | Novel cancer antigens and antibodies of said antigens |
WO2020154293A1 (en) | 2019-01-22 | 2020-07-30 | Bristol-Myers Squibb Company | Antibodies against il-7r alpha subunit and uses thereof |
WO2020154540A1 (en) | 2019-01-23 | 2020-07-30 | Millennium Pharmaceuticals, Inc. | Anti-cd38 antibodies |
WO2020152290A1 (en) | 2019-01-23 | 2020-07-30 | Encefa | Cd31 competitors and uses thereof |
WO2020152081A1 (en) | 2019-01-22 | 2020-07-30 | Innate Pharma | Treatment of t cell lymphoma |
US10745680B2 (en) | 2015-08-03 | 2020-08-18 | Bioverativ Therapeutics Inc. | Factor IX fusion proteins and methods of making and using same |
US10745487B2 (en) | 2016-03-22 | 2020-08-18 | Bionomics Limited | Method of treating cancer by administering an anti-LGR5 monoclonal antibody |
US10745467B2 (en) | 2010-03-26 | 2020-08-18 | The Trustees Of Dartmouth College | VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders |
US10751414B2 (en) | 2016-09-19 | 2020-08-25 | Celgene Corporation | Methods of treating psoriasis using PD-1 binding antibodies |
EP3698807A1 (en) | 2005-01-21 | 2020-08-26 | Genentech, Inc. | Fixed dosing of her antibodies |
EP3701971A1 (en) | 2014-03-14 | 2020-09-02 | Daniel J. Capon | Compounds useful in preparing hybrid immunoglobulin containing non-peptidyl linkage |
US10767232B2 (en) | 2014-11-03 | 2020-09-08 | Genentech, Inc. | Methods and biomarkers for predicting efficacy and evaluation of an OX40 agonist treatment |
US10766958B2 (en) | 2016-09-19 | 2020-09-08 | Celgene Corporation | Methods of treating vitiligo using PD-1 binding antibodies |
WO2020180712A1 (en) | 2019-03-01 | 2020-09-10 | Merrimack Pharmaceuticals, Inc. | Anti-tnfr2 antibodies and uses thereof |
WO2020180733A1 (en) | 2019-03-01 | 2020-09-10 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof |
US10774145B2 (en) | 2015-06-17 | 2020-09-15 | Allakos Inc. | Methods and compositions for treating fibrotic diseases |
WO2020183418A1 (en) | 2019-03-14 | 2020-09-17 | Janssen Biotech, Inc. | Manufacturing methods for producing anti-il12/il23 antibody compositions |
US10781254B2 (en) | 2010-03-26 | 2020-09-22 | The Trustees Of Dartmouth College | VISTA regulatory T cell mediator protein, VISTA binding agents and use thereof |
WO2020188466A1 (en) | 2019-03-18 | 2020-09-24 | Janssen Biotech, Inc. | Method of treating psoriasis in pediatric subjects with anti-il12/il23 antibody |
WO2020189748A1 (en) | 2019-03-19 | 2020-09-24 | 中外製薬株式会社 | Antigen-binding molecule containing antigen-binding domain of which binding activity to antigen is changed depending on mta, and library for obtaining said antigen-binding domain |
US10793633B2 (en) | 2011-09-30 | 2020-10-06 | Dana-Farber Cancer Institute, Inc. | Therapeutic peptides |
WO2020206063A1 (en) | 2019-04-03 | 2020-10-08 | Genzyme Corporation | Anti-alpha beta tcr binding polypeptides with reduced fragmentation |
US10799589B2 (en) | 2013-03-13 | 2020-10-13 | Buzzard Pharmaceuticals AB | Chimeric cytokine formulations for ocular delivery |
WO2020208177A1 (en) | 2019-04-11 | 2020-10-15 | Argenx Bvba | ANTI-IgE ANTIBODIES |
WO2020213724A1 (en) | 2019-04-19 | 2020-10-22 | 中外製薬株式会社 | Chimeric receptor recognizing modification site of antibody |
WO2020214748A1 (en) | 2019-04-18 | 2020-10-22 | Bristol-Myers Squibb Company | Ipilimumab variants with enhanced specificity for binding at low ph |
WO2020214867A1 (en) | 2019-04-17 | 2020-10-22 | Alpine Immune Sciences, Inc. | Methods and uses of variant icos ligand (icosl) fusion proteins |
KR20200121900A (en) | 2011-03-30 | 2020-10-26 | 추가이 세이야쿠 가부시키가이샤 | Method for altering plasma retention and immunogenicity of antigen-binding molecule |
US10822402B2 (en) | 2015-06-24 | 2020-11-03 | Hoffmann-La Roche Inc. | Humanized anti-tau(pS422) antibodies and methods of use |
US10836830B2 (en) | 2015-12-02 | 2020-11-17 | Agenus Inc. | Antibodies and methods of use thereof |
EP3738981A1 (en) | 2014-01-24 | 2020-11-18 | NGM Biopharmaceuticals, Inc. | Antibodies binding beta klotho domain 2 and methods of use thereof |
WO2020230899A1 (en) | 2019-05-15 | 2020-11-19 | 協和キリン株式会社 | Bispecific antibody binding to cd40 and fap |
WO2020230901A1 (en) | 2019-05-15 | 2020-11-19 | 協和キリン株式会社 | Bispecific antibody capable of binding to cd40 and gpc3 |
WO2020236792A1 (en) | 2019-05-21 | 2020-11-26 | Novartis Ag | Cd19 binding molecules and uses thereof |
WO2020236797A1 (en) | 2019-05-21 | 2020-11-26 | Novartis Ag | Variant cd58 domains and uses thereof |
WO2020236841A2 (en) | 2019-05-20 | 2020-11-26 | Novartis Ag | Antibody drug conjugates having linkers comprising hydrophilic groups |
WO2020236795A2 (en) | 2019-05-21 | 2020-11-26 | Novartis Ag | Trispecific binding molecules against bcma and uses thereof |
US10858686B2 (en) | 2010-05-27 | 2020-12-08 | Merck Sharp & Dohme Corp. | Method for preparing antibodies having improved properties |
WO2020246563A1 (en) | 2019-06-05 | 2020-12-10 | 中外製薬株式会社 | Antibody cleavage site-binding molecule |
US10865248B2 (en) | 2015-04-07 | 2020-12-15 | Genentech, Inc. | Antigen binding complex having agonistic activity and methods of use |
WO2020250915A1 (en) | 2019-06-10 | 2020-12-17 | 中外製薬株式会社 | Anti-t cell antigen-binding molecule to be used in combination with cytokine inhibitor |
WO2021006328A1 (en) | 2019-07-10 | 2021-01-14 | Chugai Seiyaku Kabushiki Kaisha | Claudin-6 binding molecules and uses thereof |
WO2021005232A1 (en) | 2019-07-11 | 2021-01-14 | Umc Utrecht Holding B.V. | Intranasal administration of neutralising antiviral antibodies |
WO2021009263A1 (en) | 2019-07-16 | 2021-01-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antibodies having specificity for cd38 and uses thereof |
WO2021011681A1 (en) | 2019-07-15 | 2021-01-21 | Bristol-Myers Squibb Company | Antibodies against human trem-1 and uses thereof |
WO2021011678A1 (en) | 2019-07-15 | 2021-01-21 | Bristol-Myers Squibb Company | Anti-trem-1 antibodies and uses thereof |
WO2021010326A1 (en) | 2019-07-12 | 2021-01-21 | 中外製薬株式会社 | Anti-mutation type fgfr3 antibody and use therefor |
US10899836B2 (en) | 2016-02-12 | 2021-01-26 | Janssen Pharmaceutica Nv | Method of identifying anti-VISTA antibodies |
WO2021014389A1 (en) | 2019-07-24 | 2021-01-28 | H. Lundbeck A/S | Anti-mglur5 antibodies and uses thereof |
WO2021021837A2 (en) | 2019-07-29 | 2021-02-04 | Compugen Ltd. | Anti-pvrig antibodies formulations and uses thereof |
WO2021017892A1 (en) | 2019-07-26 | 2021-02-04 | 上海复宏汉霖生物技术股份有限公司 | Method and composition for anti-cd73 antibodies and variants |
WO2021021605A1 (en) | 2019-07-26 | 2021-02-04 | Vanderbilt University | Human monoclonal antibodies to enterovirus d68 |
WO2021024133A2 (en) | 2019-08-06 | 2021-02-11 | Glaxosmithkline Intellectual Property Development Limited | Biopharmacuetical compositions and related methods |
WO2021030488A1 (en) | 2019-08-12 | 2021-02-18 | Bienvenue David Leonard | 4-1bb and ox40 binding proteins and related compositions and methods, antibodies against 4-1bb, antibodies against ox40 |
US10934359B2 (en) | 2016-04-21 | 2021-03-02 | Abbvie Stemcentrx Llc | Anti-BMPR1B antibodies and methods of use |
US10933115B2 (en) | 2012-06-22 | 2021-03-02 | The Trustees Of Dartmouth College | VISTA antagonist and methods of use |
US10934344B2 (en) | 2006-03-31 | 2021-03-02 | Chugai Seiyaku Kabushiki Kaisha | Methods of modifying antibodies for purification of bispecific antibodies |
WO2021042019A1 (en) | 2019-08-30 | 2021-03-04 | Agenus Inc. | Anti-cd96 antibodies and methods of use thereof |
US10941205B2 (en) | 2015-10-02 | 2021-03-09 | Hoffmann-La Roche Inc. | Bispecific anti-human A-beta/human transferrin receptor antibodies and methods of use |
EP3789403A1 (en) | 2014-11-11 | 2021-03-10 | MedImmune Limited | Therapeutic combinations comprising anti-cd73 antibodies and a2a receptor inhibitor and uses thereof |
US10947269B2 (en) | 2013-08-08 | 2021-03-16 | Bioverativ Therapeutics Inc. | Purification of chimeric FVIII molecules |
US10954301B2 (en) | 2015-12-14 | 2021-03-23 | Macrogenics, Inc. | Bispecific molecules having immunoreactivity with PD-1 and CTLA-4, and methods of use thereof |
WO2021055698A1 (en) | 2019-09-19 | 2021-03-25 | Bristol-Myers Squibb Company | Antibodies binding to vista at acidic ph |
WO2021053560A1 (en) | 2019-09-18 | 2021-03-25 | Novartis Ag | Combination therapy with entpd2 and cd73 antibodies |
WO2021053559A1 (en) | 2019-09-18 | 2021-03-25 | Novartis Ag | Entpd2 antibodies, combination therapies, and methods of using the antibodies and combination therapies |
US10961311B2 (en) | 2016-04-15 | 2021-03-30 | Macrogenics, Inc. | B7-H3 binding molecules, antibody drug conjugates thereof and methods of use thereof |
WO2021062323A1 (en) | 2019-09-26 | 2021-04-01 | Stcube & Co. | Antibodies specific to glycosylated ctla-4 and methods of use thereof |
WO2021067389A1 (en) | 2019-09-30 | 2021-04-08 | Bioverativ Therapeutics Inc. | Lentiviral vector formulations |
WO2021072277A1 (en) | 2019-10-09 | 2021-04-15 | Stcube & Co. | Antibodies specific to glycosylated lag3 and methods of use thereof |
US10995148B2 (en) | 2014-03-19 | 2021-05-04 | Genzyme Corporation | Site-specific glycoengineering of targeting moieties |
US11001643B2 (en) | 2014-09-26 | 2021-05-11 | Chugai Seiyaku Kabushiki Kaisha | Cytotoxicity-inducing therapeutic agent |
WO2021091605A1 (en) | 2019-11-04 | 2021-05-14 | Compugen Ltd. | Combination therapy with anti-pvrig antibodies formulations and anti-pd-1 antibodies |
US11008561B2 (en) | 2014-06-30 | 2021-05-18 | Bioverativ Therapeutics Inc. | Optimized factor IX gene |
US11009509B2 (en) | 2015-06-24 | 2021-05-18 | Janssen Pharmaceutica Nv | Anti-VISTA antibodies and fragments |
US11014987B2 (en) | 2013-12-24 | 2021-05-25 | Janssen Pharmaceutics Nv | Anti-vista antibodies and fragments, uses thereof, and methods of identifying same |
KR20210068061A (en) | 2018-09-28 | 2021-06-08 | 추가이 세이야쿠 가부시키가이샤 | Antigen-binding molecule comprising a modified antibody variable region |
KR20210068079A (en) | 2018-09-28 | 2021-06-08 | 추가이 세이야쿠 가부시키가이샤 | antigen binding molecule capable of binding to CD3 and CD137 but not simultaneously |
WO2021113831A1 (en) | 2019-12-05 | 2021-06-10 | Compugen Ltd. | Anti-pvrig and anti-tigit antibodies for enhanced nk-cell based tumor killing |
WO2021116119A1 (en) | 2019-12-09 | 2021-06-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antibodies having specificity to her4 and uses thereof |
US11046784B2 (en) | 2006-03-31 | 2021-06-29 | Chugai Seiyaku Kabushiki Kaisha | Methods for controlling blood pharmacokinetics of antibodies |
EP3842457A1 (en) | 2015-09-09 | 2021-06-30 | Novartis AG | Thymic stromal lymphopoietin (tslp)-binding molecules and methods of using the molecules |
WO2021131021A1 (en) | 2019-12-27 | 2021-07-01 | 中外製薬株式会社 | Anti-ctla-4 antibody and use thereof |
US11053308B2 (en) | 2016-08-05 | 2021-07-06 | Chugai Seiyaku Kabushiki Kaisha | Method for treating IL-8-related diseases |
WO2021140202A1 (en) | 2020-01-08 | 2021-07-15 | argenx BV | Methods for treating pemphigus disorders |
US11072666B2 (en) | 2016-03-14 | 2021-07-27 | Chugai Seiyaku Kabushiki Kaisha | Cell injury inducing therapeutic drug for use in cancer therapy |
US11072653B2 (en) | 2015-06-08 | 2021-07-27 | Macrogenics, Inc. | LAG-3-binding molecules and methods of use thereof |
WO2021158938A1 (en) | 2020-02-06 | 2021-08-12 | Bristol-Myers Squibb Company | Il-10 and uses thereof |
WO2021162098A1 (en) | 2020-02-14 | 2021-08-19 | 協和キリン株式会社 | Bispecific antibody that binds to cd3 |
WO2021163265A1 (en) | 2020-02-11 | 2021-08-19 | Vanderbilt University | Human monoclonal antibodies to severe acute respiratory syndrome coronavirus 2 (sars-cov- 2) |
US11098105B2 (en) | 2013-05-31 | 2021-08-24 | Zymeworks Inc. | Heteromultimers with reduced or silenced effector function |
WO2021174034A1 (en) | 2020-02-28 | 2021-09-02 | Genzyme Corporation | Modified binding polypeptides for optimized drug conjugation |
US11117975B2 (en) | 2013-04-29 | 2021-09-14 | Teva Pharmaceuticals Australia Pty Ltd | Anti-CD38 antibodies and fusions to attenuated interferon alpha-2B |
US11123426B2 (en) | 2014-06-11 | 2021-09-21 | The Trustees Of Dartmouth College | Use of vista agonists and antagonists to suppress or enhance humoral immunity |
WO2021194861A1 (en) | 2020-03-23 | 2021-09-30 | Genentech, Inc. | Biomarkers for predicting response to il-6 antagonist in covid-19 pneumonia |
WO2021195513A1 (en) | 2020-03-27 | 2021-09-30 | Novartis Ag | Bispecific combination therapy for treating proliferative diseases and autoimmune disorders |
WO2021195385A1 (en) | 2020-03-26 | 2021-09-30 | Vanderbilt University | HUMAN MONOCLONAL ANTIBODIES TO SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-GoV-2) |
WO2021194865A1 (en) | 2020-03-23 | 2021-09-30 | Genentech, Inc. | Method for treating pneumonia, including covid-19 pneumonia, with an il6 antagonist |
WO2021195418A1 (en) | 2020-03-26 | 2021-09-30 | Vanderbilt University | Human monoclonal antibodies to severe acute respiratory syndrome coronavirus 2 (sars-cov-2) |
WO2021194860A1 (en) | 2020-03-23 | 2021-09-30 | Genentech, Inc. | Tocilizumab and remdesivir combination therapy for covid-19 pneumonia |
WO2021202235A1 (en) | 2020-04-01 | 2021-10-07 | University Of Rochester | Monoclonal antibodies against the hemagglutinin (ha) and neuraminidase (na) of influenza h3n2 viruses |
WO2021201087A1 (en) | 2020-03-31 | 2021-10-07 | Chugai Seiyaku Kabushiki Kaisha | Method for producing multispecific antigen-binding molecules |
EP3892294A1 (en) | 2013-08-28 | 2021-10-13 | AbbVie Stemcentrx LLC | Site-specific antibody conjugation methods and compositions |
WO2021204179A1 (en) | 2020-04-09 | 2021-10-14 | Suzhou Abogen Biosciences Co., Ltd. | Nucleic acid vaccines for coronavirus |
WO2021207449A1 (en) | 2020-04-09 | 2021-10-14 | Merck Sharp & Dohme Corp. | Affinity matured anti-lap antibodies and uses thereof |
US11154615B2 (en) | 2014-11-11 | 2021-10-26 | Chugai Seiyaku Kabushiki Kaisha | Library of antigen-binding molecules including modified antibody variable region |
WO2021214277A1 (en) | 2020-04-24 | 2021-10-28 | F. Hoffmann-La Roche Ag | Enzyme and pathway modulation with sulfhydryl compounds and their derivatives |
WO2021222935A2 (en) | 2020-04-28 | 2021-11-04 | The Rockefeller University | Neutralizing anti-sars-cov-2 antibodies and methods of use thereof |
WO2021222181A2 (en) | 2020-04-27 | 2021-11-04 | The Regents Of The University Of California | Isoform-independent antibodies to lipoprotein(a) |
US11168125B2 (en) | 2003-05-06 | 2021-11-09 | Bioverativ Therapeutics Inc. | Immunoglobulin chimeric monomer-dimer hybrids |
WO2021226553A2 (en) | 2020-05-08 | 2021-11-11 | Alpine Immune Sciences, Inc. | April and baff inhibitory immunomodulatory proteins with and without a t cell inhibitory protein and methods of use thereof |
WO2021228956A1 (en) | 2020-05-12 | 2021-11-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | New method to treat cutaneous t-cell lymphomas and tfh derived lymphomas |
WO2021231732A1 (en) | 2020-05-15 | 2021-11-18 | Bristol-Myers Squibb Company | Antibodies to garp |
US11180557B2 (en) | 2012-06-22 | 2021-11-23 | King's College London | Vista modulators for diagnosis and treatment of cancer |
WO2021234402A2 (en) | 2020-05-21 | 2021-11-25 | Mabsolve Limited | Modified immunoglobulin fc regions |
WO2021233834A1 (en) | 2020-05-17 | 2021-11-25 | Astrazeneca Uk Limited | Sars-cov-2 antibodies and methods of selecting and using the same |
WO2021234160A2 (en) | 2020-05-22 | 2021-11-25 | Formycon Ag | Ace2 fusion proteins and uses thereof |
US11186638B2 (en) | 2011-09-12 | 2021-11-30 | Genzyme Corporation | Anti-αβTCR antibody |
WO2021238886A1 (en) | 2020-05-27 | 2021-12-02 | Staidson (Beijing) Biopharmaceuticals Co., Ltd. | Antibodies specifically recognizing nerve growth factor and uses thereof |
WO2021251438A1 (en) | 2020-06-10 | 2021-12-16 | 株式会社バイカ・セラピュティクス | Fusion protein containing erythropoietin polypeptide |
US11203638B2 (en) | 2017-05-05 | 2021-12-21 | Allakos Inc. | Methods and compositions for treating perennial allergic conjunctivitis and keratoconjunctivitis |
WO2021256555A1 (en) | 2020-06-19 | 2021-12-23 | 中外製薬株式会社 | Anti-t cell antigen-binding molecule for use in combination with angiogenesis inhibitor |
US11208632B2 (en) | 2016-04-26 | 2021-12-28 | R.P. Scherer Technologies, Llc | Antibody conjugates and methods of making and using the same |
US11208480B2 (en) | 2014-06-27 | 2021-12-28 | Innate Pharma | Multispecific antigen binding proteins |
WO2021262791A1 (en) | 2020-06-25 | 2021-12-30 | Merck Sharp & Dohme Corp. | High affinity antibodies targeting tau phosphorylated at serine 413 |
WO2022006153A1 (en) | 2020-06-29 | 2022-01-06 | Resolve Therapeutics, Llc | Treatment of sjogren's syndrome with nuclease fusion proteins |
US11230605B2 (en) * | 2015-07-22 | 2022-01-25 | Inatherys | Anti-TfR antibodies and their use in treating proliferative and inflammatory disorders |
WO2022025220A1 (en) | 2020-07-31 | 2022-02-03 | 中外製薬株式会社 | Pharmaceutical composition including cell expressing chimeric receptor |
US11242393B2 (en) | 2018-03-23 | 2022-02-08 | Bristol-Myers Squibb Company | Antibodies against MICA and/or MICB and uses thereof |
US11242392B2 (en) | 2013-12-24 | 2022-02-08 | Janssen Pharmaceutica Nv | Anti-vista antibodies and fragments |
WO2022031978A1 (en) | 2020-08-06 | 2022-02-10 | Bioverativ Usa Inc. | Inflammatory cytokines and fatigue in subject with a complement mediated disease |
WO2022034044A1 (en) | 2020-08-10 | 2022-02-17 | Astrazeneca Uk Limited | Sars-cov-2 antibodies for treatment and prevention of covid-19 |
US11253590B2 (en) | 2015-12-02 | 2022-02-22 | Stsciences, Inc. | Antibodies specific to glycosylated BTLA (B- and T- lymphocyte attenuator) |
US11254748B2 (en) | 2005-04-15 | 2022-02-22 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
WO2022040345A1 (en) | 2020-08-18 | 2022-02-24 | Cephalon, Inc. | Anti-par-2 antibodies and methods of use thereof |
WO2022045276A1 (en) | 2020-08-28 | 2022-03-03 | 中外製薬株式会社 | Heterodimer fc polypeptide |
WO2022047316A1 (en) | 2020-08-28 | 2022-03-03 | Sana Biotechnology, Inc. | Modified anti-viral binding agents |
US11267868B2 (en) | 2013-04-02 | 2022-03-08 | Chugai Seiyaku Kabushiki Kaisha | Fc region variant |
US11267883B2 (en) | 2016-12-21 | 2022-03-08 | Cephalon, Inc. | Antibodies that specifically bind to human IL-15 and uses thereof |
US11274157B2 (en) | 2017-01-12 | 2022-03-15 | Eureka Therapeutics, Inc. | Constructs targeting histone H3 peptide/MHC complexes and uses thereof |
US11274151B2 (en) | 2020-03-31 | 2022-03-15 | Chugai Seiyaku Kabushiki Kaisha | CD3-targeting and DLL3-targeting multispecific antigen-binding molecules and uses thereof |
WO2022060412A1 (en) | 2020-09-17 | 2022-03-24 | Genentech, Inc. | Results of empacta: a randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of tocilizumab in hospitalized patients with covid-19 pneumonia |
WO2022069940A1 (en) | 2020-09-30 | 2022-04-07 | Compugen Ltd. | Combination therapy with anti-pvrig antibodies formulations, anti-tigit antibodies, and anti-pd-1 antibodies |
WO2022076606A1 (en) | 2020-10-06 | 2022-04-14 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
WO2022076952A1 (en) | 2020-10-06 | 2022-04-14 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
WO2022084915A1 (en) | 2020-10-22 | 2022-04-28 | Janssen Biotech, Inc. | Proteins comprising delta-like ligand 3 (dll3) antigen binding domains and their uses |
WO2022090469A2 (en) | 2020-10-29 | 2022-05-05 | Formycon Ag | Ace2 fusion proteins and uses thereof |
WO2022090801A2 (en) | 2020-10-26 | 2022-05-05 | Compugen Ltd. | Pvrl2 and/or pvrig as biomarkers for treatment |
WO2022097061A1 (en) | 2020-11-06 | 2022-05-12 | Novartis Ag | Anti-cd19 agent and b cell targeting agent combination therapy for treating b cell malignancies |
WO2022098870A1 (en) | 2020-11-04 | 2022-05-12 | The Rockefeller University | Neutralizing anti-sars-cov-2 antibodies |
WO2022097060A1 (en) | 2020-11-06 | 2022-05-12 | Novartis Ag | Cd19 binding molecules and uses thereof |
US11332541B2 (en) | 2018-06-09 | 2022-05-17 | Boehringer Ingelheim International Gmbh | Multi-specific binding proteins for cancer treatment |
US11332533B2 (en) | 2007-09-26 | 2022-05-17 | Chugai Seiyaku Kabushiki Kaisha | Modified antibody constant region |
US11352426B2 (en) | 2015-09-21 | 2022-06-07 | Aptevo Research And Development Llc | CD3 binding polypeptides |
WO2022119976A1 (en) | 2020-12-01 | 2022-06-09 | Aptevo Research And Development Llc | Heterodimeric psma and cd3-binding bispecific antibodies |
US11359028B2 (en) | 2016-11-09 | 2022-06-14 | Agenus Inc. | Anti-OX40 antibodies and anti-GITR antibodies |
US11359009B2 (en) | 2015-12-25 | 2022-06-14 | Chugai Seiyaku Kabushiki Kaisha | Anti-myostatin antibodies and methods of use |
WO2022125941A1 (en) | 2020-12-11 | 2022-06-16 | Iovance Biotherapeutics, Inc. | Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with braf inhibitors and/or mek inhibitors |
WO2022123316A1 (en) | 2020-12-09 | 2022-06-16 | Takeda Pharmaceutical Company Limited | Compositions of guanylyl cyclase c (gcc) antigen binding agents and methods of use thereof |
WO2022123307A1 (en) | 2020-12-09 | 2022-06-16 | Takeda Pharmaceutical Company Limited | Compositions of guanylyl cyclase c (gcc) antigen binding agents and methods of use thereof |
US11365239B2 (en) | 2020-03-20 | 2022-06-21 | Tsb Therapeutics (Beijing) Co., Ltd. | Anti-SARS-COV-2 antibodies and uses thereof |
WO2022133140A1 (en) | 2020-12-17 | 2022-06-23 | Iovance Biotherapeutics, Inc. | Treatment with tumor infiltrating lymphocyte therapies in combination with ctla-4 and pd-1 inhibitors |
WO2022130182A1 (en) | 2020-12-14 | 2022-06-23 | Novartis Ag | Reversal binding agents for anti-natriuretic peptide receptor 1 (npr1) antibodies and uses thereof |
WO2022133149A1 (en) | 2020-12-17 | 2022-06-23 | Iovance Biotherapeutics, Inc. | Treatment of cancers with tumor infiltrating lymphocytes |
WO2022147196A2 (en) | 2020-12-31 | 2022-07-07 | Iovance Biotherapeutics, Inc. | Devices and processes for automated production of tumor infiltrating lymphocytes |
US11384149B2 (en) | 2013-08-09 | 2022-07-12 | Macrogenics, Inc. | Bi-specific monovalent Fc diabodies that are capable of binding CD32B and CD79b and uses thereof |
US11384144B2 (en) | 2015-05-22 | 2022-07-12 | Memorial Sloan-Kettering Cancer Center | T cell receptor-like antibodies specific for a PRAME peptide |
WO2022155324A1 (en) | 2021-01-15 | 2022-07-21 | The Rockefeller University | Neutralizing anti-sars-cov-2 antibodies |
US11401348B2 (en) | 2009-09-02 | 2022-08-02 | Xencor, Inc. | Heterodimeric Fc variants |
WO2022165260A1 (en) | 2021-01-29 | 2022-08-04 | Iovance Biotherapeutics, Inc. | Methods of making modified tumor infiltrating lymphocytes and their use in adoptive cell therapy |
WO2022165266A1 (en) | 2021-01-28 | 2022-08-04 | Compugen Ltd. | Anti-pvrig antibodies formulations and uses thereof |
WO2022165275A2 (en) | 2021-01-28 | 2022-08-04 | Compugen Ltd. | Combination therapy with anti-pvrig antibodies formulations and anti-pd-1-antibodies |
WO2022172085A2 (en) | 2021-02-15 | 2022-08-18 | Takeda Pharmaceutical Company Limited | Cell therapy compositions and methods for modulating tgf-b signaling |
WO2022184854A2 (en) | 2021-03-03 | 2022-09-09 | Formycon Ag | Formulations of ace2 fc fusion proteins |
WO2022187272A1 (en) | 2021-03-01 | 2022-09-09 | Xilio Development, Inc. | Combination of masked ctla4 and pd1/pdl1 antibodies for treating cancer |
WO2022187741A2 (en) | 2021-03-05 | 2022-09-09 | Iovance Biotherapeutics, Inc. | Tumor storage and cell culture compositions |
WO2022187270A1 (en) | 2021-03-01 | 2022-09-09 | Xilio Development, Inc. | Combination of ctla4 and pd1/pdl1 antibodies for treating cancer |
WO2022190034A1 (en) | 2021-03-12 | 2022-09-15 | Janssen Biotech, Inc. | Method of treating psoriatic arthritis patients with inadequate response to tnf therapy with anti-il23 specific antibody |
WO2022190033A1 (en) | 2021-03-12 | 2022-09-15 | Janssen Biotech, Inc. | Safe and effective method of treating psoriatic arthritis with anti-il23 specific antibody |
US11447564B2 (en) | 2017-04-26 | 2022-09-20 | Eureka Therapeutics, Inc. | Constructs specifically recognizing glypican 3 and uses thereof |
WO2022198141A1 (en) | 2021-03-19 | 2022-09-22 | Iovance Biotherapeutics, Inc. | Methods for tumor infiltrating lymphocyte (til) expansion related to cd39/cd69 selection and gene knockout in tils |
WO2022204155A1 (en) | 2021-03-23 | 2022-09-29 | Iovance Biotherapeutics, Inc. | Cish gene editing of tumor infiltrating lymphocytes and uses of same in immunotherapy |
WO2022201122A1 (en) | 2021-03-26 | 2022-09-29 | Janssen Biotech, Inc. | Humanized antibodies against paired helical filament tau and uses thereof |
WO2022204564A2 (en) | 2021-03-25 | 2022-09-29 | Iovance Biotherapeutics, Inc. | Methods and compositions for t-cell coculture potency assays and use with cell therapy products |
WO2022200525A1 (en) | 2021-03-26 | 2022-09-29 | Innate Pharma | Multispecific proteins comprising an nkp46-binding site, a cancer antgienge binding site fused to a cytokine for nk cell engaging |
WO2022212645A1 (en) | 2021-03-31 | 2022-10-06 | Bioverativ Usa Inc. | Reducing surgery-associated hemolysis in cold agglutinin disease patients |
WO2022212876A1 (en) | 2021-04-02 | 2022-10-06 | The Regents Of The University Of California | Antibodies against cleaved cdcp1 and uses thereof |
US11466093B2 (en) | 2015-07-27 | 2022-10-11 | The General Hospital Corporation | Antibody derivatives with conditionally enabled effector function |
US11472889B2 (en) | 2017-10-14 | 2022-10-18 | Cytomx Therapeutics, Inc. | Antibodies, activatable antibodies, bispecific antibodies, and bispecific activatable antibodies and methods of use thereof |
US11471488B2 (en) | 2016-07-28 | 2022-10-18 | Alpine Immune Sciences, Inc. | CD155 variant immunomodulatory proteins and uses thereof |
WO2022225981A2 (en) | 2021-04-19 | 2022-10-27 | Iovance Biotherapeutics, Inc. | Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies |
US11485782B2 (en) | 2018-03-14 | 2022-11-01 | Beijing Xuanyi Pharmasciences Co., Ltd. | Anti-claudin 18.2 antibodies |
US11485790B2 (en) | 2014-04-07 | 2022-11-01 | Chugai Seiyaku Kabushiki Kaisha | Immunoactivating antigen-binding molecule |
WO2022236335A1 (en) | 2021-05-07 | 2022-11-10 | Alpine Immune Sciences, Inc. | Methods of dosing and treatment with a taci-fc fusion immunomodulatory protein |
WO2022235867A2 (en) | 2021-05-06 | 2022-11-10 | The Rockefeller University | Neutralizing anti-sars- cov-2 antibodies and methods of use thereof |
US11505605B2 (en) | 2014-05-13 | 2022-11-22 | Chugai Seiyaku Kabushiki Kaisha | T cell-redirected antigen-binding molecule for cells having immunosuppression function |
WO2022245754A1 (en) | 2021-05-17 | 2022-11-24 | Iovance Biotherapeutics, Inc. | Pd-1 gene-edited tumor infiltrating lymphocytes and uses of same in immunotherapy |
WO2022248870A1 (en) | 2021-05-28 | 2022-12-01 | Glaxosmithkline Intellectual Property Development Limited | Combination therapies for treating cancer |
WO2022253756A1 (en) | 2021-06-01 | 2022-12-08 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of b cell depleting agents for the treatment of rheumatic heart disease |
WO2022258662A1 (en) | 2021-06-09 | 2022-12-15 | Innate Pharma | Multispecific proteins binding to nkp46, a cytokine receptor, a tumour antigen and cd16a |
WO2022258678A1 (en) | 2021-06-09 | 2022-12-15 | Innate Pharma | Multispecific proteins binding to nkp30, a cytokine receptor, a tumour antigen and cd16a |
WO2022261417A1 (en) | 2021-06-11 | 2022-12-15 | Genentech, Inc. | Method for treating chronic obstructive pulmonary disease with an st2 antagonist |
WO2022258673A1 (en) | 2021-06-09 | 2022-12-15 | Innate Pharma | Multispecific antibodies binding to cd20, nkp46, cd16 and conjugated to il-2 |
WO2022258691A1 (en) | 2021-06-09 | 2022-12-15 | Innate Pharma | Multispecific proteins binding to nkg2d, a cytokine receptor, a tumour antigen and cd16a |
US11529416B2 (en) | 2012-09-07 | 2022-12-20 | Kings College London | Vista modulators for diagnosis and treatment of cancer |
WO2022263357A1 (en) | 2021-06-14 | 2022-12-22 | Argenx Iip Bv | Anti-il-9 antibodies and methods of use thereof |
WO2022269451A1 (en) | 2021-06-22 | 2022-12-29 | Novartis Ag | Bispecific antibodies for use in treatment of hidradenitis suppurativa |
WO2023275621A1 (en) | 2021-07-01 | 2023-01-05 | Compugen Ltd. | Anti-tigit and anti-pvrig in monotherapy and combination treatments |
WO2023281466A1 (en) | 2021-07-09 | 2023-01-12 | Janssen Biotech, Inc. | Manufacturing methods for producing anti-il12/il23 antibody compositions |
WO2023283611A1 (en) | 2021-07-08 | 2023-01-12 | Staidson Biopharma Inc. | Antibodies specifically recognizing tnfr2 and uses thereof |
WO2023284714A1 (en) | 2021-07-14 | 2023-01-19 | 舒泰神(北京)生物制药股份有限公司 | Antibody that specifically recognizes cd40 and application thereof |
WO2023004074A2 (en) | 2021-07-22 | 2023-01-26 | Iovance Biotherapeutics, Inc. | Method for cryopreservation of solid tumor fragments |
WO2023009716A1 (en) | 2021-07-28 | 2023-02-02 | Iovance Biotherapeutics, Inc. | Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with kras inhibitors |
WO2023010060A2 (en) | 2021-07-27 | 2023-02-02 | Novab, Inc. | Engineered vlrb antibodies with immune effector functions |
WO2023012669A2 (en) | 2021-08-03 | 2023-02-09 | Glaxosmithkline Intellectual Property Development Limited | Biopharmaceutical compositions and stable isotope labeling peptide mapping method |
US11584793B2 (en) | 2015-06-24 | 2023-02-21 | Hoffmann-La Roche Inc. | Anti-transferrin receptor antibodies with tailored affinity |
US11591388B2 (en) | 2019-06-07 | 2023-02-28 | argenx BV | Pharmaceutical formulations of FcRn inhibitors suitable for subcutaneous administration |
US11590223B2 (en) | 2018-08-31 | 2023-02-28 | Regeneron Pharmaceuticals, Inc. | Dosing strategy that mitigates cytokine release syndrome for therapeutic antibodies |
WO2023027177A1 (en) | 2021-08-26 | 2023-03-02 | 協和キリン株式会社 | Bispecific antibody that binds to cd116 and cd131 |
WO2023039488A1 (en) | 2021-09-09 | 2023-03-16 | Iovance Biotherapeutics, Inc. | Processes for generating til products using pd-1 talen knockdown |
EP4155321A1 (en) | 2021-06-04 | 2023-03-29 | Chugai Seiyaku Kabushiki Kaisha | Anti-ddr2 antibodies and uses thereof |
WO2023049862A1 (en) | 2021-09-24 | 2023-03-30 | Iovance Biotherapeutics, Inc. | Expansion processes and agents for tumor infiltrating lymphocytes |
US11618784B2 (en) | 2016-07-19 | 2023-04-04 | Teva Pharmaceuticals Australia Pty Ltd. | Anti-CD47 combination therapy |
WO2023056362A1 (en) | 2021-09-30 | 2023-04-06 | Seagen Inc. | B7-h4 antibody-drug conjugates for the treatment of cancer |
EP4162950A1 (en) | 2021-10-08 | 2023-04-12 | Suzhou Abogen Biosciences Co., Ltd. | Nucleic acid vaccines for coronavirus |
WO2023057893A1 (en) | 2021-10-05 | 2023-04-13 | Glaxosmithkline Intellectual Property Development Limited | Combination therapies for treating cancer |
WO2023064958A1 (en) | 2021-10-15 | 2023-04-20 | Compugen Ltd. | Combination therapy with anti-pvrig antibodies formulations, anti-tigit antibodies, and anti-pd-1 antibodies |
WO2023073615A1 (en) | 2021-10-29 | 2023-05-04 | Janssen Biotech, Inc. | Methods of treating crohn's disease with anti-il23 specific antibody |
WO2023077015A2 (en) | 2021-10-27 | 2023-05-04 | Iovance Biotherapeutics, Inc. | Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy |
RU2795592C2 (en) * | 2018-01-26 | 2023-05-05 | Джензим Корпорейшн | Fc OPTIONS WITH INCREASED FcRn BINDING AND PROLONGED HALF-LIFE |
US11642398B2 (en) | 2013-03-15 | 2023-05-09 | Bioverativ Therapeutics Inc. | Factor IX polypeptide formulations |
WO2023079086A1 (en) | 2021-11-05 | 2023-05-11 | Astrazeneca Uk Limited | Composition for treatment and prevention of covid-19 |
US11649293B2 (en) | 2015-11-18 | 2023-05-16 | Chugai Seiyaku Kabushiki Kaisha | Method for enhancing humoral immune response |
US11649285B2 (en) | 2016-08-03 | 2023-05-16 | Bio-Techne Corporation | Identification of VSIG3/VISTA as a novel immune checkpoint and use thereof for immunotherapy |
US11648317B2 (en) | 2018-04-13 | 2023-05-16 | Genentech, Inc. | Stable anti-CD79B immunoconjugate formulations |
US11649262B2 (en) | 2015-12-28 | 2023-05-16 | Chugai Seiyaku Kabushiki Kaisha | Method for promoting efficiency of purification of Fc region-containing polypeptide |
WO2023086803A1 (en) | 2021-11-10 | 2023-05-19 | Iovance Biotherapeutics, Inc. | Methods of expansion treatment utilizing cd8 tumor infiltrating lymphocytes |
WO2023084488A1 (en) | 2021-11-15 | 2023-05-19 | Janssen Biotech, Inc. | Methods of treating crohn's disease with anti-il23 specific antibody |
WO2023091968A1 (en) | 2021-11-17 | 2023-05-25 | Disc Medicine, Inc. | Methods for treating anemia of kidney disease |
US11660340B2 (en) | 2015-11-18 | 2023-05-30 | Chugai Seiyaku Kabushiki Kaisha | Combination therapy using T cell redirection antigen binding molecule against cell having immunosuppressing function |
WO2023094507A1 (en) | 2021-11-24 | 2023-06-01 | Formycon Ag | Improved ace2 fusion proteins |
WO2023095000A1 (en) | 2021-11-23 | 2023-06-01 | Janssen Biotech, Inc. | Method of treating ulcerative colitis with anti-il23 specific antibody |
WO2023094571A1 (en) | 2021-11-25 | 2023-06-01 | Formycon Ag | Stabilization of ace2 fusion proteins |
US11680104B2 (en) | 2015-09-02 | 2023-06-20 | Immutep S.A.S. | Anti-LAG-3 antibodies |
WO2023114951A1 (en) | 2021-12-17 | 2023-06-22 | Viiv Healthcare Company | Combination therapies for hiv infections and uses thereof |
US11708404B2 (en) | 2014-05-16 | 2023-07-25 | Ablynx N.V. | Immunoglobulin variable domains |
WO2023139107A1 (en) | 2022-01-18 | 2023-07-27 | argenx BV | Galectin-10 antibodies |
EP4219550A1 (en) | 2018-11-02 | 2023-08-02 | Oklahoma Medical Research Foundation | Monoclonal antibodies to eltd1 and uses thereof |
WO2023147488A1 (en) | 2022-01-28 | 2023-08-03 | Iovance Biotherapeutics, Inc. | Cytokine associated tumor infiltrating lymphocytes compositions and methods |
WO2023147399A1 (en) | 2022-01-27 | 2023-08-03 | The Rockefeller University | Broadly neutralizing anti-sars-cov-2 antibodies targeting the n-terminal domain of the spike protein and methods of use thereof |
WO2023147486A1 (en) | 2022-01-28 | 2023-08-03 | Iovance Biotherapeutics, Inc. | Tumor infiltrating lymphocytes engineered to express payloads |
EP4223783A2 (en) | 2012-09-12 | 2023-08-09 | Genzyme Corporation | Fc containing polypeptides with altered glycosylation and reduced effector function |
WO2023170290A1 (en) | 2022-03-11 | 2023-09-14 | Janssen Pharmaceutica Nv | Multispecific antibodies and uses thereof |
WO2023170291A1 (en) | 2022-03-11 | 2023-09-14 | Janssen Pharmaceutica Nv | Multispecific antibodies and uses thereof |
WO2023170295A1 (en) | 2022-03-11 | 2023-09-14 | Janssen Pharmaceutica Nv | Multispecific antibodies and uses thereof |
WO2023172883A1 (en) | 2022-03-07 | 2023-09-14 | Alpine Immune Sciences, Inc. | Immunomodulatory proteins of variant cd80 polypeptides, cell therapies thereof and related methods and uses |
US11760807B2 (en) | 2014-05-08 | 2023-09-19 | Chugai Seiyaku Kabushiki Kaisha | GPC3-targeting drug which is administered to patient responsive to GPC3-targeting drug therapy |
EP4245374A2 (en) | 2022-03-18 | 2023-09-20 | Compugen Ltd. | Pvrl2 and/or pvrig as biomarkers for treatment |
WO2023178192A1 (en) | 2022-03-15 | 2023-09-21 | Compugen Ltd. | Il-18bp antagonist antibodies and their use in monotherapy and combination therapy in the treatment of cancer |
EP4249066A2 (en) | 2014-12-23 | 2023-09-27 | Bristol-Myers Squibb Company | Antibodies to tigit |
WO2023187407A1 (en) | 2022-04-01 | 2023-10-05 | Bradcode Limited | Human monoclonal antibodies binding to sars-cov-2 and methods of use thereof |
WO2023187707A1 (en) | 2022-03-30 | 2023-10-05 | Janssen Biotech, Inc. | Method of treating mild to moderate psoriasis with il-23 specific antibody |
WO2023187657A1 (en) | 2022-03-30 | 2023-10-05 | Novartis Ag | Methods of treating disorders using anti-natriuretic peptide receptor 1 (npr1) antibodies |
WO2023196877A1 (en) | 2022-04-06 | 2023-10-12 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
US11787857B2 (en) | 2018-02-02 | 2023-10-17 | Bio-Techne Corporation | Compounds that modulate the interaction of VISTA and VSIG3 and methods of making and using |
WO2023201369A1 (en) | 2022-04-15 | 2023-10-19 | Iovance Biotherapeutics, Inc. | Til expansion processes using specific cytokine combinations and/or akti treatment |
WO2023209177A1 (en) | 2022-04-29 | 2023-11-02 | Astrazeneca Uk Limited | Sars-cov-2 antibodies and methods of using the same |
WO2023212304A1 (en) | 2022-04-29 | 2023-11-02 | 23Andme, Inc. | Antigen binding proteins |
WO2023220608A1 (en) | 2022-05-10 | 2023-11-16 | Iovance Biotherapeutics, Inc. | Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with an il-15r agonist |
US11820830B2 (en) | 2004-07-20 | 2023-11-21 | Xencor, Inc. | Optimized Fc variants |
WO2023223265A1 (en) | 2022-05-18 | 2023-11-23 | Janssen Biotech, Inc. | Method for evaluating and treating psoriatic arthritis with il23 antibody |
WO2023242362A1 (en) | 2022-06-15 | 2023-12-21 | argenx BV | Fcrn/antigen-binding molecules and methods of use |
WO2023245048A1 (en) | 2022-06-15 | 2023-12-21 | Bioverativ Usa Inc. | Anti-complement c1s antibody formulation |
WO2023250507A1 (en) | 2022-06-24 | 2023-12-28 | Bioverativ Usa Inc. | Methods for treating complement-mediated diseases |
US11858980B2 (en) | 2016-08-02 | 2024-01-02 | Visterra, Inc. | Engineered polypeptides and uses thereof |
US11866476B2 (en) | 2018-09-27 | 2024-01-09 | Xilio Development, Inc. | Masked IL-2-Fc fusion polypeptides |
WO2024011114A1 (en) | 2022-07-06 | 2024-01-11 | Iovance Biotherapeutics, Inc. | Devices and processes for automated production of tumor infiltrating lymphocytes |
WO2024020407A1 (en) | 2022-07-19 | 2024-01-25 | Staidson Biopharma Inc. | Antibodies specifically recognizing b- and t-lymphocyte attenuator (btla) and uses thereof |
WO2024020579A1 (en) | 2022-07-22 | 2024-01-25 | Bristol-Myers Squibb Company | Antibodies binding to human pad4 and uses thereof |
WO2024026386A1 (en) | 2022-07-27 | 2024-02-01 | Cephalon Llc | Anti-tl1a antibody formulations |
WO2024026496A1 (en) | 2022-07-28 | 2024-02-01 | Compugen Ltd. | Combination therapy with anti-pvrig antibodies formulations and anti-pd-1 antibodies |
WO2024026395A1 (en) | 2022-07-27 | 2024-02-01 | Cephalon Llc | Anti-tl1a antibodies for the treatment of ulcerative colitis and crohn's disease |
US11891432B2 (en) | 2018-03-15 | 2024-02-06 | Chugai Seiyaku Kabushiki Kaisha | Anti-dengue virus antibodies having cross-reactivity to Zika virus and methods of use |
WO2024030758A1 (en) | 2022-08-01 | 2024-02-08 | Iovance Biotherapeutics, Inc. | Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies |
KR20240024255A (en) | 2021-06-25 | 2024-02-23 | 추가이 세이야쿠 가부시키가이샤 | Use of anti-CTLA-4 antibodies |
KR20240024213A (en) | 2021-06-25 | 2024-02-23 | 추가이 세이야쿠 가부시키가이샤 | Anti-CTLA-4 antibody |
WO2024042112A1 (en) | 2022-08-25 | 2024-02-29 | Glaxosmithkline Intellectual Property Development Limited | Antigen binding proteins and uses thereof |
WO2024044675A1 (en) | 2022-08-25 | 2024-02-29 | Beigene, Ltd. | Methods of cancer treatment using anti-pd1 antibodies in combination with anti-tim3 antibodies |
WO2024050524A1 (en) | 2022-09-01 | 2024-03-07 | University Of Georgia Research Foundation, Inc. | Compositions and methods for directing apolipoprotein l1 to induce mammalian cell death |
WO2024052503A1 (en) | 2022-09-08 | 2024-03-14 | Institut National de la Santé et de la Recherche Médicale | Antibodies having specificity to ltbp2 and uses thereof |
US11939383B2 (en) | 2018-03-02 | 2024-03-26 | Five Prime Therapeutics, Inc. | B7-H4 antibodies and methods and use thereof |
WO2024061930A1 (en) | 2022-09-22 | 2024-03-28 | Institut National de la Santé et de la Recherche Médicale | New method to treat and diagnose peripheral t-cell lymphoma (ptcl) |
WO2024062074A1 (en) | 2022-09-21 | 2024-03-28 | Sanofi Biotechnology | Humanized anti-il-1r3 antibody and methods of use |
US11952422B2 (en) | 2017-12-05 | 2024-04-09 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule comprising altered antibody variable region binding CD3 and CD137 |
WO2024077018A2 (en) | 2022-10-04 | 2024-04-11 | Alpine Immune Sciences, Inc. | Methods and uses of taci-fc fusion immunomodulatory protein |
EP4360714A2 (en) | 2016-09-21 | 2024-05-01 | Nextcure, Inc. | Antibodies for siglec-15 and methods of use thereof |
WO2024089609A1 (en) | 2022-10-25 | 2024-05-02 | Ablynx N.V. | Glycoengineered fc variant polypeptides with enhanced effector function |
WO2024098024A1 (en) | 2022-11-04 | 2024-05-10 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof |
WO2024098027A1 (en) | 2022-11-04 | 2024-05-10 | Iovance Biotherapeutics, Inc. | Methods for tumor infiltrating lymphocyte (til) expansion related to cd39/cd103 selection |
US11993661B2 (en) | 2018-06-18 | 2024-05-28 | Eureka Therapeutics, Inc. | Constructs targeting prostate-specific membrane antigen (PSMA) and uses thereof |
WO2024110905A1 (en) | 2022-11-24 | 2024-05-30 | Beigene, Ltd. | Anti-cea antibody drug conjugates and methods of use |
WO2024112571A2 (en) | 2022-11-21 | 2024-05-30 | Iovance Biotherapeutics, Inc. | Two-dimensional processes for the expansion of tumor infiltrating lymphocytes and therapies therefrom |
WO2024112711A2 (en) | 2022-11-21 | 2024-05-30 | Iovance Biotherapeutics, Inc. | Methods for assessing proliferation potency of gene-edited t cells |
WO2024110898A1 (en) | 2022-11-22 | 2024-05-30 | Janssen Biotech, Inc. | Method of treating ulcerative colitis with anti-il23 specific antibody |
EP4382120A1 (en) | 2022-12-05 | 2024-06-12 | Institut Regional du Cancer de Montpellier | Anti-slc1a4 monoclonal antibodies and uses thereof |
EP4386084A1 (en) | 2022-12-14 | 2024-06-19 | Formycon AG | Improved ace2 fusion proteins |
Families Citing this family (565)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7132100B2 (en) | 2002-06-14 | 2006-11-07 | Medimmune, Inc. | Stabilized liquid anti-RSV antibody formulations |
US8946387B2 (en) | 2002-08-14 | 2015-02-03 | Macrogenics, Inc. | FcγRIIB specific antibodies and methods of use thereof |
US8968730B2 (en) | 2002-08-14 | 2015-03-03 | Macrogenics Inc. | FcγRIIB specific antibodies and methods of use thereof |
JP4685764B2 (en) * | 2003-04-10 | 2011-05-18 | アボット バイオセラピューティクス コーポレイション | Modification of antibody FcRn binding affinity or serum half-life by mutagenesis |
KR100973564B1 (en) * | 2003-05-02 | 2010-08-03 | 젠코어 인코포레이티드 | OPTIMIZED Fc VARIANTS AND METHODS FOR THEIR GENERATION |
US8101720B2 (en) * | 2004-10-21 | 2012-01-24 | Xencor, Inc. | Immunoglobulin insertions, deletions and substitutions |
WO2005100402A1 (en) * | 2004-04-13 | 2005-10-27 | F.Hoffmann-La Roche Ag | Anti-p-selectin antibodies |
KR100545720B1 (en) * | 2004-05-31 | 2006-01-24 | 메덱스젠 주식회사 | Glycosylated Immunoglobulin and Immunoadhesin comprising the same |
MX2007000404A (en) * | 2004-07-12 | 2008-03-04 | Macrogenics Inc | Identification and engineering of antibodies with variant fc regions and methods of using the same. |
US20070135620A1 (en) * | 2004-11-12 | 2007-06-14 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US8029783B2 (en) * | 2005-02-02 | 2011-10-04 | Genentech, Inc. | DR5 antibodies and articles of manufacture containing same |
US20100104564A1 (en) * | 2005-03-29 | 2010-04-29 | Genevieve Hansen | Altered Antibody Fc Regions and Uses Thereof |
ES2388932T3 (en) | 2005-12-02 | 2012-10-19 | Genentech, Inc. | Binding polypeptides and uses thereof |
JP5298021B2 (en) * | 2006-10-12 | 2013-09-25 | ジェネンテック, インコーポレイテッド | Antibodies against lymphotoxin-α |
CA2671264C (en) | 2006-11-30 | 2015-11-24 | Research Development Foundation | Improved immunoglobulin libraries |
US20080127996A1 (en) * | 2006-12-04 | 2008-06-05 | Weinhold Dennis G | Method and apparatus to remediate an acid and/or liquid spill |
BRPI0809042B1 (en) | 2007-03-22 | 2021-08-31 | Biogen Ma Inc. | ISOLATED CD154-BINDING PROTEIN, ITS USE, AND COMPOSITION |
US8629245B2 (en) * | 2007-05-01 | 2014-01-14 | Research Development Foundation | Immunoglobulin Fc libraries |
ES2659517T3 (en) | 2007-05-30 | 2018-03-16 | Xencor, Inc. | Methods and compositions for inhibiting cells expressing CD32B |
EP4119579A1 (en) * | 2007-05-31 | 2023-01-18 | Genmab A/S | Stable igg4 antibodies |
CN104761641A (en) * | 2007-06-12 | 2015-07-08 | Ac免疫有限公司 | Humanized antibodies to amyloid beta |
CA2692392A1 (en) * | 2007-06-29 | 2009-01-08 | Centocor Ortho Biotech Inc. | Anti- mcp-1 antibodies, compositions, methods and uses |
AU2008311366B2 (en) * | 2007-10-05 | 2015-03-12 | Ac Immune S.A. | Use of anti-amyloid beta antibody in ocular diseases |
US20110123530A1 (en) * | 2008-03-31 | 2011-05-26 | Arron Joseph R | Compositions and methods for treating and diagnosing asthma |
MX2010011955A (en) * | 2008-04-29 | 2011-01-21 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof. |
NZ589436A (en) | 2008-06-03 | 2012-12-21 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
MX2010013239A (en) | 2008-06-03 | 2011-02-24 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof. |
CN102149825B (en) | 2008-07-08 | 2015-07-22 | Abbvie公司 | Prostaglandin E2 dual variable domain immunoglobulins and uses thereof |
TW201016233A (en) * | 2008-07-15 | 2010-05-01 | Genentech Inc | Methods of treating autoimmune diseases using CD4 antibodies |
EP2408817B1 (en) | 2009-03-20 | 2016-03-16 | F.Hoffmann-La Roche Ag | Bispecific anti-her antibodies |
ES2363358B1 (en) | 2009-04-03 | 2012-06-21 | FUNDACIÓ INSTITUT DE RECERCA HOSPITAL UNIVERSITARI VALL D'HEBRON (Titular al | THERAPEUTIC AGENTS FOR THE TREATMENT OF DISEASES ASSOCIATED WITH AN INDESEABLE CELLULAR PROLIFERATION. |
BRPI1010297A2 (en) | 2009-04-07 | 2017-06-06 | Roche Glycart Ag | trivalent bispecific antibodies. |
BRPI1012195A2 (en) * | 2009-05-01 | 2018-04-24 | Abbott Lab | double variable domain immunoglobulins and their uses |
US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
WO2011008517A2 (en) * | 2009-06-30 | 2011-01-20 | Research Development Foundation | Immunoglobulin fc polypeptides |
JP2013507928A (en) * | 2009-10-15 | 2013-03-07 | アボット・ラボラトリーズ | Dual variable domain immunoglobulins and uses thereof |
UY32979A (en) | 2009-10-28 | 2011-02-28 | Abbott Lab | IMMUNOGLOBULINS WITH DUAL VARIABLE DOMAIN AND USES OF THE SAME |
EA030792B1 (en) * | 2009-11-30 | 2018-09-28 | Янссен Байотек, Инк | ANTIBODY Fc MUTANTS WITH ABLATED EFFECTOR FUNCTIONS |
WO2011091078A2 (en) | 2010-01-19 | 2011-07-28 | Xencor, Inc. | Antibody fc variants with enhanced complement activity |
US9556249B2 (en) | 2010-02-18 | 2017-01-31 | Genentech, Inc. | Neuregulin antagonists and use thereof in treating cancer |
US9260529B2 (en) | 2010-02-24 | 2016-02-16 | The University Of Washington Through Its Center For Commercialization | Molecules that bind CD180, compositions and methods of use |
RU2587625C2 (en) | 2010-03-24 | 2016-06-20 | Дженентек, Инк. | Anti-lrp6 antibodies |
EP2371860A1 (en) | 2010-04-05 | 2011-10-05 | Fundació Privada Institut d'Investigació Oncològica de Vall d'Hebron | Antibody recognising human leukemia inhibitory factor (LIF) and use of anti-LIF antibodies in the treatment of diseases associated with unwanted cell proliferation |
WO2011147834A1 (en) | 2010-05-26 | 2011-12-01 | Roche Glycart Ag | Antibodies against cd19 and uses thereof |
JP5940061B2 (en) | 2010-06-18 | 2016-06-29 | ジェネンテック, インコーポレイテッド | Anti-AXL antibodies and methods of use |
WO2011161119A1 (en) | 2010-06-22 | 2011-12-29 | F. Hoffmann-La Roche Ag | Antibodies against insulin-like growth factor i receptor and uses thereof |
WO2011161189A1 (en) | 2010-06-24 | 2011-12-29 | F. Hoffmann-La Roche Ag | Anti-hepsin antibodies and methods of use |
CN103097418A (en) | 2010-07-09 | 2013-05-08 | 霍夫曼-拉罗奇有限公司 | Anti-neuropilin antibodies and methods of us |
WO2012010582A1 (en) | 2010-07-21 | 2012-01-26 | Roche Glycart Ag | Anti-cxcr5 antibodies and methods of use |
WO2012012759A2 (en) | 2010-07-22 | 2012-01-26 | The Regents Of The University Of California | Anti-tumor antigen antibodies and methods of use |
WO2012018790A2 (en) | 2010-08-03 | 2012-02-09 | Abbott Laboratories | Dual variable domain immunoglobulins and uses thereof |
JP2013541501A (en) | 2010-08-03 | 2013-11-14 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | Biomarkers for chronic lymphocytic leukemia (CLL) |
WO2012017003A1 (en) | 2010-08-05 | 2012-02-09 | F. Hoffmann-La Roche Ag | Anti-mhc antibody anti-viral cytokine fusion protein |
RU2584597C2 (en) | 2010-08-13 | 2016-05-20 | Рош Гликарт Аг | Antibodies against a2 tenastin-c and methods for use thereof |
JP2013537416A (en) | 2010-08-13 | 2013-10-03 | メディミューン リミテッド | Monomer polypeptide containing mutant Fc region and method of use |
MA34519B1 (en) | 2010-08-13 | 2013-09-02 | Roche Glycart Ag | ANTI-FAP ANTIBODIES AND METHODS OF USE |
WO2012022734A2 (en) | 2010-08-16 | 2012-02-23 | Medimmune Limited | Anti-icam-1 antibodies and methods of use |
RU2013110874A (en) | 2010-08-25 | 2014-09-27 | Ф.Хоффманн-Ля Рош Аг | ANTIBODIES AGAINST IL-18R1 AND THEIR APPLICATION |
CN103260639A (en) | 2010-08-26 | 2013-08-21 | Abbvie公司 | Dual variable domain immunoglobulins and uses thereof |
JP2013537966A (en) | 2010-08-31 | 2013-10-07 | ジェネンテック, インコーポレイテッド | Biomarkers and methods of treatment |
WO2012030842A2 (en) | 2010-09-03 | 2012-03-08 | Academia Sinica | Anti-c-met antibody and methods of use thereof |
RU2600444C2 (en) | 2010-10-13 | 2016-10-20 | Янссен Байотек, Инк. | Human oncostatin m antibodies and methods of use thereof |
WO2012054084A2 (en) * | 2010-10-20 | 2012-04-26 | Oxford Biotherapeutics Ltd. | Antibodies |
EP2638070B1 (en) | 2010-11-10 | 2016-10-19 | F.Hoffmann-La Roche Ag | Methods and compositions for neural disease immunotherapy |
MX352789B (en) | 2010-12-16 | 2017-12-08 | Genentech Inc | Diagnosis and treatments relating to th2 inhibition. |
US8911732B2 (en) | 2010-12-20 | 2014-12-16 | Genentech, Inc. | Anti-mesothelin antibodies and immunoconjugates |
JP2014511106A (en) | 2010-12-22 | 2014-05-08 | ジェネンテック, インコーポレイテッド | Anti-PCSK9 antibody and method of use |
CN102128937B (en) * | 2010-12-31 | 2014-05-28 | 江苏华冠生物技术股份有限公司 | Evaluating and monitoring method for effect of desensitization therapy, detection kit of allergen specificity IgG4 antibody and preparation method thereof |
US8952132B2 (en) | 2011-02-07 | 2015-02-10 | Research Development Foundation | Engineered immunoglobulin FC polypeptides |
WO2012116927A1 (en) | 2011-02-28 | 2012-09-07 | F. Hoffmann-La Roche Ag | Monovalent antigen binding proteins |
RU2607038C2 (en) | 2011-02-28 | 2017-01-10 | Ф. Хоффманн-Ля Рош Аг | Antigen-binding proteins |
MX342240B (en) | 2011-04-07 | 2016-09-21 | Genentech Inc | Anti-fgfr4 antibodies and methods of use. |
KR20140059168A (en) | 2011-04-21 | 2014-05-15 | 더 리젠츠 오브 더 유니버시티 오브 콜로라도, 어 바디 코포레이트 | Compositions and methods for the treatment of neuromyelitis optica |
WO2012146630A1 (en) | 2011-04-29 | 2012-11-01 | F. Hoffmann-La Roche Ag | N-terminal acylated polypeptides, methods for their production and uses thereof |
ES2567276T3 (en) | 2011-05-12 | 2016-04-21 | Genentech, Inc. | LC-MS / MS method of monitoring multiple reactions to detect therapeutic antibodies in animal samples using frame-changing peptides |
EP3219730A1 (en) | 2011-05-16 | 2017-09-20 | F. Hoffmann-La Roche AG | Fgfr1 agonists and methods of use |
US9561274B2 (en) | 2011-06-07 | 2017-02-07 | University Of Hawaii | Treatment and prevention of cancer with HMGB1 antagonists |
WO2012170740A2 (en) | 2011-06-07 | 2012-12-13 | University Of Hawaii | Biomarker of asbestos exposure and mesothelioma |
AU2012269075B2 (en) | 2011-06-15 | 2015-05-21 | F. Hoffmann-La Roche Ag | Anti-human EPO receptor antibodies and methods of use |
WO2012175508A1 (en) | 2011-06-22 | 2012-12-27 | F. Hoffmann-La Roche Ag | Removal of target cells by circulating virus-specific cytotoxic t-cells using mhc class i comprising complexes |
EP2537864B1 (en) * | 2011-06-24 | 2019-08-07 | Laboratoire Français du Fractionnement et des Biotechnologies | Fc variants with reduced effector functions |
EP2726503B1 (en) | 2011-06-30 | 2019-09-04 | Compugen Ltd. | Polypeptides and uses thereof for treatment of autoimmune disorders and infection |
CA2842375A1 (en) | 2011-08-17 | 2013-02-21 | Erica Jackson | Neuregulin antibodies and uses thereof |
US9309306B2 (en) | 2011-08-23 | 2016-04-12 | Roche Glycart Ag | Anti-MCSP antibodies |
BR112014005720A2 (en) | 2011-09-15 | 2017-12-12 | Genentech Inc | method of selecting and / or identifying a usp1 antagonist, uaf1 antagonist and / or an id antagonist that promotes a change in the cellular fate of said method |
JP2014534949A (en) | 2011-09-19 | 2014-12-25 | ジェネンテック, インコーポレイテッド | Combination treatment comprising C-MET antagonist and B-RAF antagonist |
SG11201401287SA (en) | 2011-10-05 | 2014-05-29 | Genentech Inc | Methods of treating liver conditions using notch2 antagonists |
AU2012322618A1 (en) | 2011-10-14 | 2014-05-29 | Genentech, Inc. | Anti-HtrA1 antibodies and methods of use |
WO2013056148A2 (en) | 2011-10-15 | 2013-04-18 | Genentech, Inc. | Methods of using scd1 antagonists |
WO2013059531A1 (en) | 2011-10-20 | 2013-04-25 | Genentech, Inc. | Anti-gcgr antibodies and uses thereof |
AR088509A1 (en) | 2011-10-28 | 2014-06-11 | Genentech Inc | THERAPEUTIC COMBINATIONS AND METHODS TO TREAT MELANOMA |
KR102168733B1 (en) | 2011-10-31 | 2020-10-23 | 추가이 세이야쿠 가부시키가이샤 | Antigen-binding molecule having regulated conjugation between heavy-chain and light-chain |
WO2013070565A1 (en) | 2011-11-07 | 2013-05-16 | Medimmune, Llc | Multispecific and multivalent binding proteins and uses thereof |
WO2013083497A1 (en) | 2011-12-06 | 2013-06-13 | F. Hoffmann-La Roche Ag | Antibody formulation |
DK2794905T3 (en) | 2011-12-20 | 2020-07-06 | Medimmune Llc | MODIFIED POLYPEPTIDES FOR BISPECIFIC ANTIBODY BASIC STRUCTURES |
WO2013096791A1 (en) | 2011-12-23 | 2013-06-27 | Genentech, Inc. | Process for making high concentration protein formulations |
BR112014015851A2 (en) | 2011-12-30 | 2019-09-24 | Abbvie Inc | double specific binding proteins directed against il-13 and / or il-17 |
WO2013109856A2 (en) | 2012-01-18 | 2013-07-25 | Genentech, Inc. | Methods of using fgf19 modulators |
EA028202B1 (en) | 2012-01-18 | 2017-10-31 | Дженентек, Инк. | Anti-lrp5 antibodies and methods of use thereof |
AU2013218017B2 (en) | 2012-02-07 | 2017-12-07 | Innate Pharma | MICA binding agents |
EP2812350B1 (en) | 2012-02-11 | 2019-04-03 | F.Hoffmann-La Roche Ag | R-spondin translocations and methods using the same |
EP2814587B1 (en) | 2012-02-15 | 2018-05-02 | F.Hoffmann-La Roche Ag | Fc-receptor based affinity chromatography |
CA2865082A1 (en) | 2012-03-27 | 2013-10-03 | Genentech, Inc. | Diagnosis and treatments relating to her3 inhibitors |
AR090549A1 (en) | 2012-03-30 | 2014-11-19 | Genentech Inc | ANTI-LGR5 AND IMMUNOCATE PLAYERS |
WO2013151762A1 (en) | 2012-04-05 | 2013-10-10 | Ac Immune S.A. | Humanized tau antibody |
CN104470544B (en) | 2012-05-01 | 2018-01-12 | 基因泰克公司 | Anti- PMEL17 antibody and immunoconjugates |
WO2013170191A1 (en) | 2012-05-11 | 2013-11-14 | Genentech, Inc. | Methods of using antagonists of nad biosynthesis from nicotinamide |
RU2625771C2 (en) | 2012-05-23 | 2017-07-18 | Дженентек, Инк. | Therapeutics selection method |
KR20150023711A (en) | 2012-06-15 | 2015-03-05 | 제넨테크, 인크. | Anti-pcsk9 antibodies, formulations, dosing, and methods of use |
CA2872184A1 (en) | 2012-07-04 | 2014-01-09 | F. Hoffmann-La Roche Ag | Anti-theophylline antibodies and methods of use |
MX358281B (en) | 2012-07-04 | 2018-08-13 | Hoffmann La Roche | Covalently linked antigen-antibody conjugates. |
WO2014006123A1 (en) | 2012-07-04 | 2014-01-09 | F. Hoffmann-La Roche Ag | Anti-biotin antibodies and methods of use |
JP6309518B2 (en) | 2012-07-05 | 2018-04-11 | ジェネンテック, インコーポレイテッド | Expression and secretion system |
MX2015000314A (en) | 2012-07-09 | 2015-04-10 | Genentech Inc | Immunoconjugates comprising anti - cd79b antibodies. |
EP2869849A1 (en) | 2012-07-09 | 2015-05-13 | Genentech, Inc. | Immunoconjugates comprising anti-cd22 antibodies |
AU2013288930A1 (en) | 2012-07-09 | 2014-12-04 | Genentech, Inc. | Immunoconjugates comprising anti-CD79b antibodies |
BR112015000439A2 (en) | 2012-07-09 | 2017-12-19 | Genentech Inc | immunoconjugate, pharmaceutical formulation and methods of treating an individual and inhibiting proliferation |
KR20210111353A (en) | 2012-11-01 | 2021-09-10 | 애브비 인코포레이티드 | Anti-vegf/dll4 dual variable domain immunoglobulins and uses thereof |
WO2014071358A2 (en) | 2012-11-05 | 2014-05-08 | Foundation Medicine, Inc. | Novel ntrk1 fusion molecules and uses thereof |
AR093378A1 (en) | 2012-11-08 | 2015-06-03 | Hoffmann La Roche | BINDING PROTEINS OF ANTIGEN HER3 OF UNION TO THE FORK b OF HER3 |
EP2919813B1 (en) | 2012-11-13 | 2018-10-24 | F.Hoffmann-La Roche Ag | Anti-hemagglutinin antibodies and methods of use |
JP6490591B2 (en) | 2012-12-10 | 2019-03-27 | バイオジェン・エムエイ・インコーポレイテッドBiogen MA Inc. | Anti-blood dendritic cell antigen 2 antibody and use thereof |
MX361076B (en) | 2012-12-21 | 2018-11-27 | Hoffmann La Roche | Disulfide-linked multivalent mhc class i comprising multi-function proteins. |
WO2014107739A1 (en) | 2013-01-07 | 2014-07-10 | Eleven Biotherapeutics, Inc. | Antibodies against pcsk9 |
EP2945652B1 (en) | 2013-01-18 | 2021-07-07 | Foundation Medicine, Inc. | Methods of treating cholangiocarcinoma |
WO2014116749A1 (en) | 2013-01-23 | 2014-07-31 | Genentech, Inc. | Anti-hcv antibodies and methods of using thereof |
BR112015018418A2 (en) | 2013-02-22 | 2017-07-18 | Hoffmann La Roche | methods for treating cancer, for increasing the effectiveness of a treatment, for postponing and / or preventing cancer development, for increasing sensitivity to a targeted therapy, to extending the sensitivity period, to extending the response duration to a targeted therapy. and pharmaceutical |
WO2014131715A1 (en) | 2013-02-26 | 2014-09-04 | Roche Glycart Ag | Anti-mcsp antibodies |
US9487587B2 (en) | 2013-03-05 | 2016-11-08 | Macrogenics, Inc. | Bispecific molecules that are immunoreactive with immune effector cells of a companion animal that express an activating receptor and cells that express B7-H3 and uses thereof |
MX2015011428A (en) | 2013-03-06 | 2016-02-03 | Genentech Inc | Methods of treating and preventing cancer drug resistance. |
US9562099B2 (en) | 2013-03-14 | 2017-02-07 | Genentech, Inc. | Anti-B7-H4 antibodies and immunoconjugates |
KR20150127203A (en) | 2013-03-14 | 2015-11-16 | 제넨테크, 인크. | Combinations of a mek inhibitor compound with an her3/egfr inhibitor compound and methods of use |
KR20150127216A (en) | 2013-03-14 | 2015-11-16 | 제넨테크, 인크. | Methods of treating cancer and preventing cancer drug resistance |
MX2015010777A (en) | 2013-03-14 | 2016-04-25 | Genentech Inc | Anti-b7-h4 antibodies and immunoconjugates. |
WO2014151006A2 (en) | 2013-03-15 | 2014-09-25 | Genentech, Inc. | Biomarkers and methods of treating pd-1 and pd-l1 related conditions |
CA2905123A1 (en) | 2013-03-15 | 2014-09-18 | Genentech, Inc. | Methods of treating cancer and preventing cancer drug resistance |
CA2903546A1 (en) | 2013-03-15 | 2014-09-25 | Biogen Ma Inc. | Treatment and prevention of acute kidney injury using anti-alpha v beta 5 antibodies |
US10035859B2 (en) | 2013-03-15 | 2018-07-31 | Biogen Ma Inc. | Anti-alpha V beta 6 antibodies and uses thereof |
JP2016517441A (en) | 2013-03-15 | 2016-06-16 | ジェネンテック, インコーポレイテッド | Anti-CRTh2 antibody and method of use |
EP3385277A1 (en) | 2013-03-15 | 2018-10-10 | F. Hoffmann-La Roche AG | Il-22 polypeptides and il-22 fc fusion proteins and methods of use |
MX2015013166A (en) | 2013-03-15 | 2015-12-11 | Abbvie Inc | Dual specific binding proteins directed against il-1 beta and il-17. |
BR112015020290A2 (en) | 2013-03-15 | 2017-10-10 | Genentech Inc | methods for treating cancer, for preventing cancer, for inhibiting proliferation, for treating a mammal therapeutically, for treating a dysfunction, for reducing spp1 protein levels, for treating a cancer therapeutically, for treating an individual, and for inhibiting cell proliferation, article, antibodies and uses |
FR3003171B1 (en) * | 2013-03-15 | 2015-04-10 | Lab Francais Du Fractionnement | NOVEL MEDICAMENTS COMPRISING AN ENHANCED ANTIBODY COMPOSITION IN MAJORITY LOAD ENFORCEMENT |
WO2014143739A2 (en) | 2013-03-15 | 2014-09-18 | Biogen Idec Ma Inc. | Anti-alpha v beta 6 antibodies and uses thereof |
JP6568514B2 (en) | 2013-03-15 | 2019-08-28 | エーシー イミューン エス.エー. | Anti-tau antibodies and methods of use |
SG11201508911PA (en) | 2013-04-29 | 2015-11-27 | Hoffmann La Roche | Human fcrn-binding modified antibodies and methods of use |
RU2687043C2 (en) | 2013-04-29 | 2019-05-06 | Ф. Хоффманн-Ля Рош Аг | Fc-RECEPTOR BINDING MODIFIED ASYMMETRIC ANTIBODIES AND METHODS OF USE |
PT3702373T (en) | 2013-09-13 | 2022-09-27 | Beigene Switzerland Gmbh | Anti-pd1 antibodies and their use as therapeutics and diagnostics |
RU2016109247A (en) | 2013-09-17 | 2017-10-19 | Дженентек, Инк. | WAYS OF APPLICATION OF ANTIBODIES TO LGR5 |
WO2015050959A1 (en) | 2013-10-01 | 2015-04-09 | Yale University | Anti-kit antibodies and methods of use thereof |
RU2683498C2 (en) | 2013-10-02 | 2019-03-28 | МЕДИММЬЮН, ЭлЭлСи | Neutralising anti-influenza a antibodies and uses thereof |
BR112016006929A2 (en) | 2013-10-11 | 2017-09-19 | Hoffmann La Roche | ANTIBODY, NUCLEIC ACID, EXPRESSION VECTOR, HOST CELL, METHODS OF PREPARING ANTIBODY, TREATMENT OF PATIENTS AND GENERATION OF AN ANTIBODY, PHARMACEUTICAL COMPOSITION AND USE OF THE ANTIBODY |
MX2016004573A (en) | 2013-10-11 | 2016-07-21 | Genentech Inc | Nsp4 inhibitors and methods of use. |
JP6677638B2 (en) | 2013-10-18 | 2020-04-08 | ジェネンテック, インコーポレイテッド | Anti-RSPO2 and / or RSPO3 antibodies and uses thereof |
JP6715767B2 (en) | 2013-10-23 | 2020-07-01 | ジェネンテック, インコーポレイテッド | Method for diagnosing and treating eosinophilic disease |
CN104623637A (en) | 2013-11-07 | 2015-05-20 | 健能隆医药技术(上海)有限公司 | Application of IL-22 dimer in preparation of intravenous injection drugs |
LT3071597T (en) | 2013-11-21 | 2020-10-12 | F. Hoffmann-La Roche Ag | Anti-alpha-synuclein antibodies and methods of use |
WO2015089344A1 (en) | 2013-12-13 | 2015-06-18 | Genentech, Inc. | Anti-cd33 antibodies and immunoconjugates |
US8986691B1 (en) | 2014-07-15 | 2015-03-24 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
EP3083692B1 (en) | 2013-12-17 | 2020-02-19 | F.Hoffmann-La Roche Ag | Methods of treating her2-positive cancers using pd-1 axis binding antagonists and anti-her2 antibodies |
CA2933881A1 (en) | 2013-12-17 | 2015-06-25 | Genentech, Inc. | Methods of treating cancer using pd-1 axis binding antagonists and an anti-cd20 antibody |
US8980273B1 (en) | 2014-07-15 | 2015-03-17 | Kymab Limited | Method of treating atopic dermatitis or asthma using antibody to IL4RA |
PT3083689T (en) | 2013-12-17 | 2020-08-27 | Genentech Inc | Anti-cd3 antibodies and methods of use |
TWI670283B (en) | 2013-12-23 | 2019-09-01 | 美商建南德克公司 | Antibodies and methods of use |
CN111228509A (en) | 2014-01-03 | 2020-06-05 | 豪夫迈·罗氏有限公司 | Bispecific anti-hapten/anti-blood brain barrier receptor antibodies, complexes thereof and their use as blood brain barrier shuttles |
MX2016008191A (en) | 2014-01-03 | 2017-11-16 | Hoffmann La Roche | Covalently linked polypeptide toxin-antibody conjugates. |
WO2015101587A1 (en) | 2014-01-03 | 2015-07-09 | F. Hoffmann-La Roche Ag | Covalently linked helicar-anti-helicar antibody conjugates and uses thereof |
CN111057147B (en) | 2014-01-06 | 2023-11-10 | 豪夫迈·罗氏有限公司 | Monovalent blood brain barrier shuttle module |
CN110903398B (en) | 2014-01-15 | 2023-08-15 | 豪夫迈·罗氏有限公司 | Fc region variants with modified FCRN and maintained protein A binding properties |
BR112016015693A2 (en) | 2014-01-24 | 2017-10-24 | Genentech Inc | Method To Treat Prostate Cancer And Antibody |
AU2015213741B2 (en) | 2014-02-08 | 2020-10-08 | Genentech, Inc. | Methods of treating Alzheimer's Disease |
EP3718563A1 (en) | 2014-02-08 | 2020-10-07 | F. Hoffmann-La Roche AG | Methods of treating alzheimer's disease |
SG10201808259TA (en) | 2014-02-12 | 2018-10-30 | Genentech Inc | Anti-jagged1 antibodies and methods of use |
CA2937556A1 (en) | 2014-02-21 | 2015-08-27 | Genentech, Inc. | Anti-il-13/il-17 bispecific antibodies and uses thereof |
US9732154B2 (en) * | 2014-02-28 | 2017-08-15 | Janssen Biotech, Inc. | Anti-CD38 antibodies for treatment of acute lymphoblastic leukemia |
NZ631007A (en) | 2014-03-07 | 2015-10-30 | Alexion Pharma Inc | Anti-c5 antibodies having improved pharmacokinetics |
WO2015140591A1 (en) | 2014-03-21 | 2015-09-24 | Nordlandssykehuset Hf | Anti-cd14 antibodies and uses thereof |
CN107002119A (en) | 2014-03-24 | 2017-08-01 | 豪夫迈·罗氏有限公司 | Treatment of cancer and the former and associating that HGF is expressed using C MET antagonists |
WO2015164615A1 (en) | 2014-04-24 | 2015-10-29 | University Of Oslo | Anti-gluten antibodies and uses thereof |
JP2017522861A (en) | 2014-05-22 | 2017-08-17 | ジェネンテック, インコーポレイテッド | Anti-GPC3 antibody and immunoconjugate |
MX2016015163A (en) | 2014-05-23 | 2017-03-03 | Genentech Inc | Mit biomarkers and methods using the same. |
KR20170010785A (en) | 2014-06-11 | 2017-02-01 | 제넨테크, 인크. | Anti-lgr5 antibodies and uses thereof |
JP2017517552A (en) | 2014-06-13 | 2017-06-29 | ジェネンテック, インコーポレイテッド | Treatment and prevention of anticancer drug resistance |
MX2016015280A (en) | 2014-06-26 | 2017-03-03 | Hoffmann La Roche | Anti-brdu antibodies and methods of use. |
KR102130600B1 (en) | 2014-07-03 | 2020-07-08 | 베이진 엘티디 | Anti-PD-L1 Antibodies and Their Use as Therapeutics and Diagnostics |
CN106488775A (en) | 2014-07-11 | 2017-03-08 | 基因泰克公司 | NOTCH approach suppresses |
MX2017000419A (en) | 2014-07-11 | 2017-08-16 | Genentech Inc | Anti-pd-l1 antibodies and diagnostic uses thereof. |
NZ766356A (en) | 2014-07-22 | 2024-02-23 | Cb Therapeutics Inc | Anti-pd-1 antibodies |
NZ766660A (en) | 2014-08-05 | 2024-02-23 | Cb Therapeutics Inc | Anti-pd-l1 antibodies |
KR20230172625A (en) | 2014-08-28 | 2023-12-22 | 바이오아트라, 인코퍼레이티드 | Conditionally active chimeric antigen receptors for modified t-cells |
CN113698485A (en) | 2014-09-12 | 2021-11-26 | 基因泰克公司 | anti-B7-H4 antibodies and immunoconjugates |
CN107108724A (en) | 2014-09-12 | 2017-08-29 | 豪夫迈·罗氏有限公司 | Cysteine engineered antibody and conjugate |
SG11201701623UA (en) | 2014-09-12 | 2017-03-30 | Genentech Inc | Anti-her2 antibodies and immunoconjugates |
TW201625690A (en) | 2014-09-12 | 2016-07-16 | 建南德克公司 | Anti-CLL-1 antibodies and immunoconjugates |
RU2727663C2 (en) | 2014-09-17 | 2020-07-22 | Дженентек, Инк. | Immunoconjugates, containing antibodies against her2 and pyrrolbenzodiazepines |
HRP20200924T8 (en) | 2014-09-23 | 2023-07-21 | F. Hoffmann - La Roche Ag | Method of using anti-cd79b immunoconjugates |
TW201629100A (en) * | 2014-10-06 | 2016-08-16 | 格納西尼有限公司 | Human IgG4 Fc polypeptide variant |
EP3207057A2 (en) | 2014-10-16 | 2017-08-23 | F. Hoffmann-La Roche AG | Anti-alpha-synuclein antibodies and methods of use |
KR102544705B1 (en) | 2014-11-05 | 2023-06-15 | 제넨테크, 인크. | Methods of producing two chain proteins in bacteria |
WO2016073791A1 (en) | 2014-11-05 | 2016-05-12 | Genentech, Inc. | Methods of producing two chain proteins in bacteria |
EP3611188B1 (en) | 2014-11-06 | 2022-05-04 | F. Hoffmann-La Roche AG | Fc-region variants with modified fcrn-binding and methods of use |
WO2016073157A1 (en) | 2014-11-06 | 2016-05-12 | Genentech, Inc. | Anti-ang2 antibodies and methods of use thereof |
KR20170076697A (en) | 2014-11-06 | 2017-07-04 | 에프. 호프만-라 로슈 아게 | Fc-region variants with modified fcrn- and protein a-binding properties |
RU2017119428A (en) | 2014-11-06 | 2018-12-06 | Дженентек, Инк. | COMBINED THERAPY, INCLUDING THE USE OF OX40-CONNECTING AGONISTS AND TIGIT INHIBITORS |
ES2877080T3 (en) | 2014-11-10 | 2021-11-16 | Medimmune Ltd | CD73-specific binding molecules and uses thereof |
WO2016077369A1 (en) | 2014-11-10 | 2016-05-19 | Genentech, Inc. | Animal model for nephropathy and agents for treating the same |
EP3218403B1 (en) | 2014-11-10 | 2020-05-13 | F.Hoffmann-La Roche Ag | Anti-interleukin-33 antibodies and uses thereof |
JP6859259B2 (en) | 2014-11-19 | 2021-04-14 | ジェネンテック, インコーポレイテッド | Antibodies to BACEl and its use for neurological disease immunotherapy |
US9382321B2 (en) * | 2014-11-26 | 2016-07-05 | Adventis Health System/Sunbelt, Inc. | Effector-deficient anti-CD32A antibodies |
ES2764111T3 (en) | 2014-12-03 | 2020-06-02 | Hoffmann La Roche | Multispecific antibodies |
DK3227336T3 (en) | 2014-12-05 | 2019-09-16 | Hoffmann La Roche | Anti-CD79b antibodies and methods for use |
WO2016094881A2 (en) | 2014-12-11 | 2016-06-16 | Abbvie Inc. | Lrp-8 binding proteins |
TW201809008A (en) | 2014-12-19 | 2018-03-16 | 日商中外製藥股份有限公司 | Anti-C5 antibodies and methods of use |
EP3247723A1 (en) | 2015-01-22 | 2017-11-29 | Chugai Seiyaku Kabushiki Kaisha | A combination of two or more anti-c5 antibodies and methods of use |
AU2016219511B2 (en) | 2015-02-09 | 2020-11-12 | Research Development Foundation | Engineered immunoglobulin Fc polypeptides displaying improved complement activation |
AU2016233398A1 (en) | 2015-03-16 | 2017-09-07 | F. Hoffmann-La Roche Ag | Methods of detecting and quantifying IL-13 and uses in diagnosing and treating Th2-associated diseases |
WO2016146833A1 (en) | 2015-03-19 | 2016-09-22 | F. Hoffmann-La Roche Ag | Biomarkers for nad(+)-diphthamide adp ribosyltransferase resistance |
AR104368A1 (en) | 2015-04-03 | 2017-07-19 | Lilly Co Eli | ANTI-CD20- / ANTI-BAFF BIESPECTIFIC ANTIBODIES |
CN115932273A (en) | 2015-04-24 | 2023-04-07 | 豪夫迈·罗氏有限公司 | Methods of identifying bacteria comprising binding polypeptides |
CN107709363A (en) | 2015-05-01 | 2018-02-16 | 基因泰克公司 | Shelter anti-cd 3 antibodies and application method |
EP3294771A1 (en) | 2015-05-11 | 2018-03-21 | H. Hoffnabb-La Roche Ag | Compositions and methods of treating lupus nephritis |
SI3294770T1 (en) | 2015-05-12 | 2021-01-29 | F. Hoffmann-La Roche Ag | Therapeutic and diagnostic methods for cancer |
MX2017014736A (en) | 2015-05-29 | 2018-03-23 | Genentech Inc | Therapeutic and diagnostic methods for cancer. |
CN107771182A (en) | 2015-05-29 | 2018-03-06 | 豪夫迈·罗氏有限公司 | The anti-Ebola virus glycoproteins antibody of humanization and application method |
JP2018516933A (en) | 2015-06-02 | 2018-06-28 | ジェネンテック, インコーポレイテッド | Compositions and methods for treating neurological disorders using anti-IL-34 antibodies |
TWI827405B (en) | 2015-06-05 | 2023-12-21 | 美商建南德克公司 | Anti-tau antibodies and methods of use |
TW201710286A (en) | 2015-06-15 | 2017-03-16 | 艾伯維有限公司 | Binding proteins against VEGF, PDGF, and/or their receptors |
JP2018524295A (en) | 2015-06-15 | 2018-08-30 | ジェネンテック, インコーポレイテッド | Antibodies and immune complexes |
US10323094B2 (en) | 2015-06-16 | 2019-06-18 | Genentech, Inc. | Humanized and affinity matured antibodies to FcRH5 and methods of use |
JP6996983B2 (en) | 2015-06-16 | 2022-02-21 | ジェネンテック, インコーポレイテッド | Anti-CLL-1 antibody and how to use |
EP3916018A1 (en) | 2015-06-16 | 2021-12-01 | Genentech, Inc. | Anti-cd3 antibodies and methods of use |
KR20180018538A (en) | 2015-06-17 | 2018-02-21 | 제넨테크, 인크. | Methods for the treatment of locally advanced or metastatic breast cancer using PD-1 axis-binding antagonists and taxanes |
KR20180012859A (en) | 2015-06-17 | 2018-02-06 | 제넨테크, 인크. | Anti-HER2 antibodies and methods of use |
ES2878316T3 (en) | 2015-06-29 | 2021-11-18 | Ventana Med Syst Inc | Materials and Procedures for Histochemical Assays for Human Pro-epiregulin and Ampheregulin |
BR112017027736A2 (en) | 2015-06-29 | 2018-10-09 | Genentech Inc | anti-cd20 type ii antibody for use in organ transplantation |
CN105384825B (en) | 2015-08-11 | 2018-06-01 | 南京传奇生物科技有限公司 | A kind of bispecific chimeric antigen receptor and its application based on single domain antibody |
CN108026180B (en) | 2015-08-28 | 2022-06-07 | 豪夫迈·罗氏有限公司 | Anti-hypusine antibodies and uses thereof |
AU2016328357B2 (en) | 2015-09-22 | 2023-03-02 | Ventana Medical Systems, Inc. | Anti-OX40 antibodies and diagnostic uses thereof |
CN108137681B (en) | 2015-09-23 | 2024-06-18 | 豪夫迈·罗氏有限公司 | Optimized variants of anti-VEGF antibodies |
EP3352791B1 (en) | 2015-09-24 | 2019-10-30 | AbVitro LLC | Hiv antibody compositions and methods of use |
MX2018003633A (en) | 2015-09-25 | 2018-08-01 | Genentech Inc | Anti-tigit antibodies and methods of use. |
AR106188A1 (en) | 2015-10-01 | 2017-12-20 | Hoffmann La Roche | ANTI-CD19 HUMANIZED HUMAN ANTIBODIES AND METHODS OF USE |
CN108602887B (en) | 2015-10-02 | 2022-06-21 | 豪夫迈·罗氏有限公司 | Bispecific antibodies specific for co-stimulatory TNF receptors |
EP3150636A1 (en) | 2015-10-02 | 2017-04-05 | F. Hoffmann-La Roche AG | Tetravalent multispecific antibodies |
RU2746409C1 (en) | 2015-10-02 | 2021-04-13 | Ф. Хоффманн-Ля Рош Аг | Pd1 antibodies and their application methods |
US10287352B2 (en) | 2015-10-02 | 2019-05-14 | Hoffman-La Roche Inc. | Bispecific antibodies specific for PD1 and TIM3 |
MA43345A (en) | 2015-10-02 | 2018-08-08 | Hoffmann La Roche | PYRROLOBENZODIAZEPINE ANTIBODY-DRUG CONJUGATES AND METHODS OF USE |
JP7074665B2 (en) | 2015-10-07 | 2022-05-24 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | Field of Invention of Tetravalent Bispecific Antibodies to Co-Stimulated TNF Receptors |
MA43354A (en) | 2015-10-16 | 2018-08-22 | Genentech Inc | CONJUGATE DRUG CONJUGATES WITH CLOUDY DISULPHIDE |
MA45326A (en) | 2015-10-20 | 2018-08-29 | Genentech Inc | CALICHEAMICIN-ANTIBODY-DRUG CONJUGATES AND METHODS OF USE |
EP3184547A1 (en) | 2015-10-29 | 2017-06-28 | F. Hoffmann-La Roche AG | Anti-tpbg antibodies and methods of use |
CN114920846A (en) | 2015-10-29 | 2022-08-19 | 豪夫迈·罗氏有限公司 | Anti-variant Fc region antibodies and methods of use |
US10421821B2 (en) | 2015-10-30 | 2019-09-24 | Genentech, Inc. | Anti-HtrA1 antibodies and methods of use thereof |
WO2017079768A1 (en) | 2015-11-08 | 2017-05-11 | Genentech, Inc. | Methods of screening for multispecific antibodies |
RU2742606C2 (en) | 2015-12-18 | 2021-02-09 | Чугаи Сейяку Кабусики Кайся | C5 antibodies and methods for using them |
KR20180097615A (en) | 2016-01-08 | 2018-08-31 | 에프. 호프만-라 로슈 아게 | Methods for the treatment of CEA-positive cancers using PD-1 axis-binding antagonists and anti-CEA / anti-CD3 bispecific antibodies |
WO2017127764A1 (en) | 2016-01-20 | 2017-07-27 | Genentech, Inc. | High dose treatments for alzheimer's disease |
CN109196121B (en) | 2016-02-29 | 2022-01-04 | 基因泰克公司 | Methods for treatment and diagnosis of cancer |
JP6943872B2 (en) | 2016-03-25 | 2021-10-06 | ジェネンテック, インコーポレイテッド | Multiple whole antibody and antibody complex drug quantification assay |
EP3865511A1 (en) | 2016-04-14 | 2021-08-18 | F. Hoffmann-La Roche AG | Anti-rspo3 antibodies and methods of use |
AU2017248766A1 (en) | 2016-04-15 | 2018-11-01 | Genentech, Inc. | Methods for monitoring and treating cancer |
WO2017181111A2 (en) | 2016-04-15 | 2017-10-19 | Genentech, Inc. | Methods for monitoring and treating cancer |
KR102459684B1 (en) | 2016-04-15 | 2022-10-26 | 바이오아트라, 인코퍼레이티드 | Anti-axl antibodies and their immunoconjugates and uses thereof |
US11510966B2 (en) | 2016-04-15 | 2022-11-29 | Evive Biotechnology (Shanghai) Ltd | Use of IL-22 in treating necrotizing enterocolitis |
KR102523682B1 (en) | 2016-05-02 | 2023-04-19 | 에프. 호프만-라 로슈 아게 | Kontolsbody - single chain target binder |
JP7089483B2 (en) | 2016-05-11 | 2022-06-22 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | Modified anti-tenascin antibody and usage |
KR20230044567A (en) | 2016-05-13 | 2023-04-04 | 바이오아트라, 인코퍼레이티드 | Anti-ror2 antibodies, antibody fragments, their immunoconjugates and uses thereof |
CN109152843A (en) | 2016-05-20 | 2019-01-04 | 豪夫迈·罗氏有限公司 | PROTAC antibody conjugates and its application method |
WO2017205741A1 (en) | 2016-05-27 | 2017-11-30 | Genentech, Inc. | Bioanalytical method for the characterization of site-specific antibody-drug conjugates |
EP3464280B1 (en) | 2016-06-06 | 2021-10-06 | F. Hoffmann-La Roche AG | Silvestrol antibody-drug conjugates and methods of use |
HUE064454T2 (en) | 2016-06-08 | 2024-03-28 | Xencor Inc | Treatment of igg4-related diseases with anti-cd19 antibodies crossbinding to cd32b |
EP3475298A1 (en) | 2016-06-24 | 2019-05-01 | H. Hoffnabb-La Roche Ag | Anti-polyubiquitin multispecific antibodies |
EP3478717B1 (en) | 2016-07-04 | 2022-01-05 | F. Hoffmann-La Roche AG | Novel antibody format |
CN109475536B (en) | 2016-07-05 | 2022-05-27 | 百济神州有限公司 | Combination of a PD-l antagonist and a RAF inhibitor for the treatment of cancer |
WO2018014260A1 (en) | 2016-07-20 | 2018-01-25 | Nanjing Legend Biotech Co., Ltd. | Multispecific antigen binding proteins and methods of use thereof |
EP3487880A1 (en) | 2016-07-25 | 2019-05-29 | Biogen MA Inc. | Anti-hspa5 (grp78) antibodies and uses thereof |
WO2018021450A1 (en) | 2016-07-29 | 2018-02-01 | 中外製薬株式会社 | Bispecific antibody exhibiting increased alternative fviii-cofactor-function activity |
WO2018027124A1 (en) | 2016-08-05 | 2018-02-08 | Medimmune, Llc | Anti-o2 antibodies and uses thereof |
WO2018029124A1 (en) | 2016-08-08 | 2018-02-15 | F. Hoffmann-La Roche Ag | Therapeutic and diagnostic methods for cancer |
WO2018031662A1 (en) | 2016-08-11 | 2018-02-15 | Genentech, Inc. | Pyrrolobenzodiazepine prodrugs and antibody conjugates thereof |
EP3497120A1 (en) * | 2016-08-12 | 2019-06-19 | Janssen Biotech, Inc. | Engineered antibodies and other fc-domain containing molecules with enhanced agonism and effector functions |
US11701357B2 (en) | 2016-08-19 | 2023-07-18 | Beigene Switzerland Gmbh | Treatment of B cell cancers using a combination comprising Btk inhibitors |
JP6976315B2 (en) | 2016-09-19 | 2021-12-08 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | Affinity chromatography based on complement factors |
PT3528838T (en) | 2016-09-23 | 2023-09-04 | Hoffmann La Roche | Uses of il-13 antagonists for treating atopic dermatitis |
EP3522933B1 (en) | 2016-10-05 | 2021-12-15 | F. Hoffmann-La Roche AG | Methods for preparing antibody drug conjugates |
CN110418851A (en) | 2016-10-06 | 2019-11-05 | 基因泰克公司 | The treatment of cancer and diagnostic method |
WO2018068201A1 (en) | 2016-10-11 | 2018-04-19 | Nanjing Legend Biotech Co., Ltd. | Single-domain antibodies and variants thereof against ctla-4 |
US11117956B2 (en) | 2016-10-19 | 2021-09-14 | Medimmune, Llc | Anti-O1 antibodies and uses thereof |
US11286295B2 (en) | 2016-10-20 | 2022-03-29 | Sanofi | Anti-CHIKV monoclonal antibodies directed against the E2 structural protein |
JP2019535250A (en) | 2016-10-29 | 2019-12-12 | ジェネンテック, インコーポレイテッド | Anti-MIC antibody and method of use |
KR20240029119A (en) | 2016-11-15 | 2024-03-05 | 제넨테크, 인크. | Dosing for treatment with anti-cd20/anti-cd3 bispecific antibodies |
TW201829463A (en) | 2016-11-18 | 2018-08-16 | 瑞士商赫孚孟拉羅股份公司 | Anti-hla-g antibodies and use thereof |
JOP20190100A1 (en) | 2016-11-19 | 2019-05-01 | Potenza Therapeutics Inc | Anti-gitr antigen-binding proteins and methods of use thereof |
EP3468991A1 (en) | 2016-11-21 | 2019-04-17 | cureab GmbH | Anti-gp73 antibodies and immunoconjugates |
JP7193457B2 (en) | 2016-12-07 | 2022-12-20 | ジェネンテック, インコーポレイテッド | Anti-TAU antibody and method of use |
CA3045294A1 (en) | 2016-12-07 | 2018-06-14 | Genentech, Inc. | Anti-tau antibodies and methods of use |
MX2019006331A (en) | 2016-12-12 | 2019-07-12 | Genentech Inc | Methods of treating cancer using anti-pd-l1 antibodies and antiandrogens. |
MX2019007376A (en) | 2016-12-19 | 2020-02-07 | Mosaic Biomedicals S L U | Antibodies against lif and uses thereof. |
WO2018115960A1 (en) | 2016-12-19 | 2018-06-28 | Mosaic Biomedicals, S.L. | Antibodies against lif and uses thereof |
MX2019006954A (en) | 2016-12-20 | 2019-08-01 | Hoffmann La Roche | Combination therapy of anti-cd20/anti-cd3 bispecific antibodies and 4-1bb (cd137) agonists. |
JOP20190134A1 (en) | 2016-12-23 | 2019-06-02 | Potenza Therapeutics Inc | Anti-neuropilin antigen-binding proteins and methods of use thereof |
AU2018206138A1 (en) | 2017-01-03 | 2019-07-11 | F. Hoffmann-La Roche Ag | Bispecific antigen binding molecules comprising anti-4-1BB clone 20H4.9 |
WO2018137681A1 (en) | 2017-01-25 | 2018-08-02 | Beigene, Ltd. | Crystalline forms of (s) -7- (1- (but-2-ynoyl) piperidin-4-yl) -2- (4-phenoxyphenyl) -4, 5, 6, 7-tetrahy dropyrazolo [1, 5-a] pyrimidine-3-carboxamide, preparation, and uses thereof |
US20190367599A1 (en) | 2017-01-31 | 2019-12-05 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical composition for use in the treatment or prevention of a c5-related disease and a method for treating or preventing a c5-related disease |
MX2019009485A (en) | 2017-02-10 | 2019-11-05 | Genentech Inc | Anti-tryptase antibodies, compositions thereof, and uses thereof. |
SG11201906961UA (en) * | 2017-02-10 | 2019-08-27 | Genmab Bv | Polypeptide variants and uses thereof |
DK3583120T3 (en) | 2017-02-17 | 2022-12-19 | Denali Therapeutics Inc | MODIFIED TRANSFERRIN RECEPTOR BINDING POLYPEPTIDES |
NZ756323A (en) | 2017-02-28 | 2022-07-01 | Seagen Inc | Cysteine mutated antibodies for conjugation |
JP7256127B2 (en) | 2017-03-01 | 2023-04-11 | ジェネンテック, インコーポレイテッド | Diagnostic and therapeutic methods for cancer |
MY201701A (en) | 2017-03-22 | 2024-03-13 | Genentech Inc | Optimized antibody compositions for treatment of ocular disorders |
MX2019011423A (en) | 2017-03-28 | 2019-11-01 | Genentech Inc | Methods of treating neurodegenerative diseases. |
JP7205995B2 (en) | 2017-03-29 | 2023-01-17 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | Bispecific antigen-binding molecules for co-stimulatory TNF receptors |
CN110573528B (en) | 2017-03-29 | 2023-06-09 | 豪夫迈·罗氏有限公司 | Bispecific antigen binding molecules to costimulatory TNF receptors |
JOP20190203A1 (en) | 2017-03-30 | 2019-09-03 | Potenza Therapeutics Inc | Anti-tigit antigen-binding proteins and methods of use thereof |
SG11201908787WA (en) | 2017-04-04 | 2019-10-30 | Hoffmann La Roche | Novel bispecific antigen binding molecules capable of specific binding to cd40 and to fap |
AU2018247794A1 (en) | 2017-04-05 | 2019-08-22 | F. Hoffmann-La Roche Ag | Bispecific antibodies specifically binding to PD1 and LAG3 |
RS63591B1 (en) | 2017-04-05 | 2022-10-31 | Hoffmann La Roche | Anti-lag3 antibodies |
EP3610042A1 (en) | 2017-04-14 | 2020-02-19 | H. Hoffnabb-La Roche Ag | Diagnostic and therapeutic methods for cancer |
PE20200150A1 (en) | 2017-04-21 | 2020-01-17 | Genentech Inc | USE OF KLK5 ANTAGONISTS FOR THE TREATMENT OF A DISEASE |
EP3615572A1 (en) | 2017-04-27 | 2020-03-04 | Tesaro Inc. | Antibody agents directed against lymphocyte activation gene-3 (lag-3) and uses thereof |
US20210087286A1 (en) | 2017-06-20 | 2021-03-25 | Amgen Inc. | Method of treating or ameliorating metabolic disorders using binding proteins for gastric inhibitory peptide receptor (gipr) in combination with glp-1 agonists |
AU2018289581A1 (en) | 2017-06-23 | 2020-01-16 | VelosBio Inc. | ROR1 antibody immunoconjugates |
CA3066518A1 (en) | 2017-06-26 | 2019-01-03 | Beigene, Ltd. | Immunotherapy for hepatocellular carcinoma |
CA3069469A1 (en) | 2017-07-21 | 2019-01-24 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
MX2020000957A (en) | 2017-07-26 | 2020-07-22 | Forty Seven Inc | Anti-sirp-alpha antibodies and related methods. |
CN107748262A (en) * | 2017-07-26 | 2018-03-02 | 东曜药业有限公司 | A kind of ELISA detection method of Fc γ RIIIA acceptors |
CN107748259A (en) * | 2017-07-26 | 2018-03-02 | 东曜药业有限公司 | A kind of ELISA detection method of FcRn acceptors |
CN107748253A (en) * | 2017-07-26 | 2018-03-02 | 东曜药业有限公司 | A kind of ELISA detection method of Fc γ RI acceptors |
CN107748258A (en) * | 2017-07-26 | 2018-03-02 | 东曜药业有限公司 | A kind of ELISA detection method of Fc γ RII acceptors |
DK3658184T3 (en) | 2017-07-27 | 2023-11-27 | Alexion Pharma Inc | HIGHLY CONCENTRATED ANTI-C5 ANTIBODY FORMULATIONS |
KR20200037366A (en) | 2017-08-11 | 2020-04-08 | 제넨테크, 인크. | Anti-CD8 antibodies and uses thereof |
AR113142A1 (en) | 2017-09-29 | 2020-01-29 | Chugai Pharmaceutical Co Ltd | MULTISPECIFIC ANTIGEN BINDING MOLECULES THAT HAVE SUBSTITUTION ACTIVITY FOR THE COFACTOR FUNCTION OF BLOOD COAGULATION FACTOR VIII (FVIII), AND PHARMACEUTICAL FORMULATIONS CONTAINING SUCH ACTIVE MOLECULE AS INGREDIENT |
CN111372950A (en) | 2017-10-12 | 2020-07-03 | 免疫苏醒公司 | VEGFR-antibody light chain fusion proteins |
CN111246885B (en) | 2017-10-20 | 2024-06-11 | 豪夫迈·罗氏有限公司 | Method for generating multispecific antibodies from monospecific antibodies |
MX2020004100A (en) | 2017-10-30 | 2020-07-24 | Hoffmann La Roche | Method for in vivo generation of multispecific antibodies from monospecific antibodies. |
CN111213059B (en) | 2017-11-06 | 2024-01-09 | 豪夫迈·罗氏有限公司 | Diagnostic and therapeutic methods for cancer |
CN111801334B (en) | 2017-11-29 | 2023-06-09 | 百济神州瑞士有限责任公司 | Treatment of indolent or invasive B-cell lymphomas using combinations comprising BTK inhibitors |
EP3502140A1 (en) | 2017-12-21 | 2019-06-26 | F. Hoffmann-La Roche AG | Combination therapy of tumor targeted icos agonists with t-cell bispecific molecules |
EP3728321A1 (en) | 2017-12-22 | 2020-10-28 | F. Hoffmann-La Roche AG | Use of pilra binding agents for treatment of a disease |
WO2019129211A1 (en) | 2017-12-28 | 2019-07-04 | Nanjing Legend Biotech Co., Ltd. | Antibodies and variants thereof against pd-l1 |
CA3082280A1 (en) | 2017-12-28 | 2019-07-04 | Nanjing Legend Biotech Co., Ltd. | Single-domain antibodies and variants thereof against tigit |
EP3732195A4 (en) | 2017-12-28 | 2022-02-09 | Chugai Seiyaku Kabushiki Kaisha | Cytotoxicity-inducing therapeutic agent |
CN111511400A (en) | 2017-12-29 | 2020-08-07 | 豪夫迈·罗氏有限公司 | anti-VEGF antibodies and methods of use thereof |
WO2019134981A1 (en) | 2018-01-05 | 2019-07-11 | Ac Immune Sa | Misfolded tdp-43 binding molecules |
WO2019137541A1 (en) | 2018-01-15 | 2019-07-18 | Nanjing Legend Biotech Co., Ltd. | Single-domain antibodies and variants thereof against pd-1 |
WO2019143636A1 (en) | 2018-01-16 | 2019-07-25 | Lakepharma, Inc. | Bispecific antibody that binds cd3 and another target |
PT3743088T (en) | 2018-01-26 | 2022-12-05 | Hoffmann La Roche | Compositions and methods of use |
MA51676A (en) | 2018-01-26 | 2021-05-05 | Hoffmann La Roche | IL-22 FC FUSION PROTEINS AND METHODS OF USE |
AU2019218959A1 (en) | 2018-02-08 | 2020-09-03 | Genentech, Inc. | Bispecific antigen-binding molecules and methods of use |
WO2019157358A1 (en) | 2018-02-09 | 2019-08-15 | Genentech, Inc. | Therapeutic and diagnostic methods for mast cell-mediated inflammatory diseases |
WO2019158645A1 (en) | 2018-02-14 | 2019-08-22 | Abba Therapeutics Ag | Anti-human pd-l2 antibodies |
AU2019226085A1 (en) | 2018-02-21 | 2020-09-17 | Genentech, Inc. | Dosing for treatment with IL-22 Fc fusion proteins |
EP3759141A1 (en) | 2018-02-26 | 2021-01-06 | F. Hoffmann-La Roche AG | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
KR20200132913A (en) | 2018-03-13 | 2020-11-25 | 에프. 호프만-라 로슈 아게 | Therapeutic combination of 4-1BB agonist and anti-CD20 antibody |
US20200040103A1 (en) | 2018-03-14 | 2020-02-06 | Genentech, Inc. | Anti-klk5 antibodies and methods of use |
JP2021518411A (en) * | 2018-03-21 | 2021-08-02 | デイナ ファーバー キャンサー インスティチュート,インコーポレイテッド | Fc variant composition and its usage |
AR115318A1 (en) | 2018-03-29 | 2020-12-23 | Genentech Inc | MODULATION OF LACTOGENIC ACTIVITY IN MAMMAL CELLS |
CN111886254B (en) | 2018-03-30 | 2023-12-08 | 南京传奇生物科技有限公司 | Single domain antibodies against LAG-3 and uses thereof |
TW202011029A (en) | 2018-04-04 | 2020-03-16 | 美商建南德克公司 | Methods for detecting and quantifying FGF21 |
AU2019251289B2 (en) | 2018-04-12 | 2024-01-18 | Fundacio Privada Institucio Catalana de Recerca i Estudis Avancats | Combination of LIF inhibitors and PD-1 axis inhibitors for use in treating cancer |
AR114789A1 (en) | 2018-04-18 | 2020-10-14 | Hoffmann La Roche | ANTI-HLA-G ANTIBODIES AND THE USE OF THEM |
AR115052A1 (en) | 2018-04-18 | 2020-11-25 | Hoffmann La Roche | MULTI-SPECIFIC ANTIBODIES AND THE USE OF THEM |
CN110464842B (en) | 2018-05-11 | 2022-10-14 | 信达生物制药(苏州)有限公司 | Formulations comprising anti-PCSK 9 antibodies and uses thereof |
SG11202011170YA (en) | 2018-05-14 | 2020-12-30 | Medimmune Ltd | Antibodies against lif and dosage forms thereof |
WO2019226658A1 (en) | 2018-05-21 | 2019-11-28 | Compass Therapeutics Llc | Multispecific antigen-binding compositions and methods of use |
JP2021526014A (en) | 2018-06-05 | 2021-09-30 | アムジエン・インコーポレーテツド | Regulation of antibody-dependent cellular cytotoxicity |
MA52300A (en) | 2018-06-18 | 2021-04-21 | Fundacio Privada Inst Dinvestigacio Oncològica De Vall Hebron | COMBINATION OF LIF INHIBITORS AND PLATINUM-BASED ANTI-NEOPLASICS AGENTS FOR USE IN THE TREATMENT OF CANCER |
MA52968A (en) | 2018-06-23 | 2021-04-28 | Hoffmann La Roche | METHODS OF TREATMENT OF LUNG CANCER USING A PD-1 AXIS ANTAGONIST, PLATINUM AGENT AND TOPOISOMERASE II INHIBITOR |
JP2021528988A (en) | 2018-07-04 | 2021-10-28 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | New bispecific agonist 4-1BB antigen-binding molecule |
BR112021000673A2 (en) | 2018-07-18 | 2021-04-20 | Genentech, Inc. | methods for treating an individual with lung cancer, kits, anti-pd-l1 antibody and compositions |
DE112019003835T5 (en) | 2018-08-01 | 2021-05-27 | Chugai Seiyaku Kabushiki Kaisha | MEDICINAL PRODUCTS FOR USE IN THE TREATMENT OR PREVENTION OF A C5-RELATED DISEASE, AND METHODS OF TREATMENT OR PREVENTION OF A C5-RELATED DISEASE |
EP3831854A4 (en) | 2018-08-03 | 2022-05-04 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule containing two antigen-binding domains that are linked to each other |
EP3608674A1 (en) | 2018-08-09 | 2020-02-12 | Regeneron Pharmaceuticals, Inc. | Methods for assessing binding affinity of an antibody variant to the neonatal fc receptor |
AR114550A1 (en) | 2018-08-10 | 2020-09-16 | Chugai Pharmaceutical Co Ltd | ANTI-CD137 ANTIGEN BINDING MOLECULES AND THEIR USES |
GB201814281D0 (en) | 2018-09-03 | 2018-10-17 | Femtogenix Ltd | Cytotoxic agents |
WO2020055900A1 (en) | 2018-09-11 | 2020-03-19 | Amgen Inc. | Methods of modulating antibody-dependent cell-mediated cytotoxicity |
WO2020061060A1 (en) | 2018-09-19 | 2020-03-26 | Genentech, Inc. | Therapeutic and diagnostic methods for bladder cancer |
EP4249917A3 (en) | 2018-09-21 | 2023-11-08 | F. Hoffmann-La Roche AG | Diagnostic methods for triple-negative breast cancer |
US11591390B2 (en) | 2018-09-27 | 2023-02-28 | Celgene Corporation | SIRP-α binding proteins and methods of use thereof |
EP3861025A1 (en) | 2018-10-01 | 2021-08-11 | F. Hoffmann-La Roche AG | Bispecific antigen binding molecules with trivalent binding to cd40 |
SG11202102477QA (en) | 2018-10-01 | 2021-04-29 | Hoffmann La Roche | Bispecific antigen binding molecules comprising anti-fap clone 212 |
WO2020081493A1 (en) | 2018-10-16 | 2020-04-23 | Molecular Templates, Inc. | Pd-l1 binding proteins |
KR20210079311A (en) | 2018-10-18 | 2021-06-29 | 제넨테크, 인크. | Diagnosis and treatment methods for sarcoma renal cancer |
JP2022506156A (en) | 2018-11-05 | 2022-01-17 | ジェネンテック, インコーポレイテッド | Method for producing double-stranded protein in prokaryotic host cell |
US20210115130A1 (en) | 2018-11-27 | 2021-04-22 | Innovent Biologics (Suzhou) Co., Ltd. | Anti-il-23p19 antibody and use thereof |
CN113260633A (en) | 2018-12-05 | 2021-08-13 | 豪夫迈·罗氏有限公司 | Diagnostic methods and compositions for cancer immunotherapy |
MX2021006573A (en) | 2018-12-06 | 2021-07-15 | Genentech Inc | Combination therapy of diffuse large b-cell lymphoma comprising an anti-cd79b immunoconjugates, an alkylating agent and an anti-cd20 antibody. |
CN113227119A (en) | 2018-12-10 | 2021-08-06 | 基因泰克公司 | Photocrosslinked peptides for site-specific conjugation to Fc-containing proteins |
BR112021010634A2 (en) | 2018-12-14 | 2021-11-16 | Boehringer Ingelheim Io Canada Inc | Antiperiostin antibodies and their uses |
CA3123503A1 (en) | 2018-12-21 | 2020-06-25 | F. Hoffmann-La Roche Ag | Antibody that binds to vegf and il-1beta and methods of use |
SG11202106116QA (en) | 2018-12-21 | 2021-07-29 | Genentech Inc | Methods of producing polypeptides using a cell line resistant to apoptosis |
KR20210111792A (en) | 2018-12-28 | 2021-09-13 | 스팍스 테라퓨틱스 인크. | Binding molecules specific for claudin 18.2, compositions and methods thereof for treating cancer and other diseases |
CN113272327A (en) | 2018-12-30 | 2021-08-17 | 豪夫迈·罗氏有限公司 | Anti-rabbit CD19 antibodies and methods of use thereof |
CA3124837A1 (en) | 2019-01-14 | 2020-07-23 | Genentech, Inc. | Methods of treating cancer with a pd-1 axis binding antagonist and an rna vaccine |
CA3124515A1 (en) | 2019-01-23 | 2020-07-30 | Genentech, Inc. | Methods of producing multimeric proteins in eukaryotic host cells |
GB201901197D0 (en) | 2019-01-29 | 2019-03-20 | Femtogenix Ltd | G-A Crosslinking cytotoxic agents |
MX2021010313A (en) | 2019-02-27 | 2021-09-23 | Genentech Inc | Dosing for treatment with anti-tigit and anti-cd20 or anti-cd38 antibodies. |
JP7402247B2 (en) | 2019-03-08 | 2023-12-20 | ジェネンテック, インコーポレイテッド | Methods for detecting and quantifying membrane-bound proteins of extracellular vesicles |
CA3130446A1 (en) | 2019-03-14 | 2020-09-17 | Genentech, Inc. | Treatment of cancer with her2xcd3 bispecific antibodies in combination with anti-her2 mab |
CN113631573B (en) | 2019-03-25 | 2024-06-04 | 国家医疗保健研究所 | Anti-Tau antibodies and their use in the manufacture of a medicament for the treatment of diseases |
JP2022527372A (en) | 2019-04-08 | 2022-06-01 | バイオジェン・エムエイ・インコーポレイテッド | Anti-integrin antibodies and their use |
US12006511B2 (en) | 2019-04-15 | 2024-06-11 | The Medical College Of Wisconsin, Inc. | Recombinant PD-L1 peptides and methods of use |
MX2021012608A (en) | 2019-04-18 | 2021-11-12 | Ac Immune Sa | Novel molecules for therapy and diagnosis. |
MX2021012692A (en) | 2019-04-19 | 2021-11-12 | Genentech Inc | Anti-mertk antibodies and their methods of use. |
AU2020270376A1 (en) | 2019-05-03 | 2021-10-07 | Genentech, Inc. | Methods of treating cancer with an anti-PD-L1 antibody |
AU2020275415A1 (en) | 2019-05-14 | 2021-11-25 | Genentech, Inc. | Methods of using anti-CD79B immunoconjugates to treat follicular lymphoma |
CA3137882A1 (en) | 2019-05-23 | 2020-11-26 | Tamara SEREDENINA | Anti-tdp-43 binding molecules and uses thereof |
US20220298230A1 (en) * | 2019-06-11 | 2022-09-22 | The Rockefeller University | Antibodies and methods for treatment of viral infections |
WO2020260326A1 (en) | 2019-06-27 | 2020-12-30 | F. Hoffmann-La Roche Ag | Novel icos antibodies and tumor-targeted antigen binding molecules comprising them |
EP4003409A1 (en) | 2019-07-31 | 2022-06-01 | F. Hoffmann-La Roche AG | Dosage and administration regimen for the treatment or prevention of c5-related diseases by the use of the anti-c5 antibody crovalimab |
WO2021019033A1 (en) | 2019-07-31 | 2021-02-04 | F. Hoffmann-La Roche Ag | Dosage and administration regimen for the treatment or prevention of c5-related diseases by the use of the anti-c5 antibody crovalimab |
CA3148740A1 (en) | 2019-08-06 | 2021-02-11 | Aprinoia Therapeutics Limited | Antibodies that bind to pathological tau species and uses thereof |
CN114787182A (en) | 2019-08-13 | 2022-07-22 | 艾佩斯瑞生物制药公司 | Engineered interleukin-2 receptor beta agonists |
WO2021050645A1 (en) | 2019-09-12 | 2021-03-18 | Genentech, Inc. | Compositions and methods of treating lupus nephritis |
BR112022004972A2 (en) | 2019-09-18 | 2022-06-28 | Genentech Inc | ANTIBODIES, ISOLATED NUCLEIC ACIDS, ISOLATED HOST CELLS, METHODS OF PRODUCTION OF AN ANTIBODY, OF PRODUCTION OF A BIESPECIFIC ANTIBODY, AND OF TREATMENT OF AN INDIVIDUAL, BIESPECIFIC ANTIBODIES, PHARMACEUTICAL COMPOSITION, ANTIBODY, BIESPECIFIC ANTIBODY OR PHARMACEUTICAL COMPOSITION OF THE ANTIBODY, USE OF A COMBINATION OF THE ANTIBODY AND METHODS TO REDUCE INFLAMMATION AND TO IMPROVE SCALING AND/OR SKIN ERUPTION AND COMBINATION FOR USE |
WO2021055694A1 (en) | 2019-09-20 | 2021-03-25 | Genentech, Inc. | Dosing for anti-tryptase antibodies |
WO2021058729A1 (en) | 2019-09-27 | 2021-04-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-müllerian inhibiting substance type i receptor antibodies and uses thereof |
EP4034560A1 (en) | 2019-09-27 | 2022-08-03 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-müllerian inhibiting substance antibodies and uses thereof |
WO2021059075A1 (en) | 2019-09-27 | 2021-04-01 | Janssen Biotech, Inc. | Anti-ceacam antibodies and uses thereof |
WO2021062085A1 (en) | 2019-09-27 | 2021-04-01 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
US20220372161A1 (en) | 2019-10-08 | 2022-11-24 | Nectin Therapeutics Ltd. | Antibodies against the poliovirus receptor (pvr) and uses thereof |
KR20220086618A (en) | 2019-10-18 | 2022-06-23 | 제넨테크, 인크. | Methods of Use of Anti-CD79b Immunoconjugates to Treat Diffuse Large B-Cell Lymphoma |
WO2021092171A1 (en) | 2019-11-06 | 2021-05-14 | Genentech, Inc. | Diagnostic and therapeutic methods for treatment of hematologic cancers |
CN115151562A (en) | 2019-12-04 | 2022-10-04 | Ac免疫有限公司 | Novel molecules for therapy and diagnosis |
JP2023504642A (en) | 2019-12-04 | 2023-02-06 | メドイミューン・リミテッド | Antibodies against LIF and uses thereof |
CN117417448A (en) | 2019-12-13 | 2024-01-19 | 基因泰克公司 | anti-LY 6G6D antibodies and methods of use |
CN113045655A (en) | 2019-12-27 | 2021-06-29 | 高诚生物医药(香港)有限公司 | anti-OX 40 antibodies and uses thereof |
WO2021142002A1 (en) | 2020-01-06 | 2021-07-15 | Vaccinex, Inc. | Anti-ccr8 antibodies and uses thereof |
CN110818795B (en) | 2020-01-10 | 2020-04-24 | 上海复宏汉霖生物技术股份有限公司 | anti-TIGIT antibodies and methods of use |
WO2021194481A1 (en) | 2020-03-24 | 2021-09-30 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
WO2022050954A1 (en) | 2020-09-04 | 2022-03-10 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
CN115397459A (en) | 2020-01-31 | 2022-11-25 | 基因泰克公司 | Method for inducing new epitope-specific T cells using PD-1 axis binding antagonists and RNA vaccines |
TW202144395A (en) | 2020-02-12 | 2021-12-01 | 日商中外製藥股份有限公司 | Anti-CD137 antigen-binding molecule for use in cancer treatment |
WO2021173844A1 (en) | 2020-02-26 | 2021-09-02 | Biograph 55, Inc. | C19 c38 bispecific antibodies |
CA3169939A1 (en) | 2020-02-28 | 2021-09-02 | Jie Xue | Anti-cd137 construct and use thereof |
CA3169910A1 (en) | 2020-02-28 | 2021-09-02 | Shanghai Henlius Biotech, Inc. | Anti-cd137 constructs, multispecific antibody and uses thereof |
IL295979A (en) | 2020-03-06 | 2022-10-01 | Ona Therapeutics S L | Anti-cd36 antibodies and their use to treat cancer |
CA3170025A1 (en) | 2020-03-13 | 2021-09-16 | Jiangsu Hengrui Pharmaceuticals Co., Ltd. | Pvrig binding protein and its medical uses |
PE20230252A1 (en) | 2020-03-13 | 2023-02-07 | Genentech Inc | ANTI-INTERLEUKIN-33 ANTIBODIES AND ITS USES FOR THEM |
IL296427A (en) | 2020-03-19 | 2022-11-01 | Genentech Inc | Isoform-selective anti-tgf-beta antibodies and methods of use |
TW202144419A (en) | 2020-03-24 | 2021-12-01 | 美商建南德克公司 | Tie2-binding agents and methods of use |
TW202202620A (en) | 2020-03-26 | 2022-01-16 | 美商建南德克公司 | Modified mammalian cells |
WO2021198034A1 (en) | 2020-03-30 | 2021-10-07 | F. Hoffmann-La Roche Ag | Antibody that binds to vegf and pdgf-b and methods of use |
AR121706A1 (en) | 2020-04-01 | 2022-06-29 | Hoffmann La Roche | OX40 AND FAP-TARGETED BSPECIFIC ANTIGEN-BINDING MOLECULES |
CN115698717A (en) | 2020-04-03 | 2023-02-03 | 基因泰克公司 | Methods of treatment and diagnosis of cancer |
WO2021207662A1 (en) | 2020-04-10 | 2021-10-14 | Genentech, Inc. | Use of il-22fc for the treatment or prevention of pneumonia, acute respiratory distress syndrome, or cytokine release syndrome |
BR112022021441A2 (en) | 2020-04-24 | 2022-12-13 | Genentech Inc | METHODS TO TREAT FOLLICULAR LYMPHOMA AND DIFFUSE LARGE B-CELL LYMPHOMA AND KITS |
WO2021222167A1 (en) | 2020-04-28 | 2021-11-04 | Genentech, Inc. | Methods and compositions for non-small cell lung cancer immunotherapy |
IL297830A (en) | 2020-05-03 | 2023-01-01 | Levena Suzhou Biopharma Co Ltd | Antibody-drug conjugates (adcs) comprising an anti-trop-2 antibody, compositions comprising such adcs, as well as methods of making and using the same |
CN116529260A (en) | 2020-06-02 | 2023-08-01 | 当康生物技术有限责任公司 | anti-CD 93 constructs and uses thereof |
TW202210515A (en) | 2020-06-02 | 2022-03-16 | 美商當康生物科技有限公司 | Anti-cd93 constructs and uses thereof |
MX2022015206A (en) | 2020-06-08 | 2023-01-05 | Hoffmann La Roche | Anti-hbv antibodies and methods of use. |
EP4165415A1 (en) | 2020-06-12 | 2023-04-19 | Genentech, Inc. | Methods and compositions for cancer immunotherapy |
AU2021293038A1 (en) | 2020-06-16 | 2023-02-02 | F. Hoffmann-La Roche Ag | Methods and compositions for treating triple-negative breast cancer |
EP4168118A1 (en) | 2020-06-18 | 2023-04-26 | Genentech, Inc. | Treatment with anti-tigit antibodies and pd-1 axis binding antagonists |
EP4169948A1 (en) | 2020-06-22 | 2023-04-26 | Innovent Biologics (Suzhou) Co., Ltd. | Anti-cd73 antibody and use thereof |
MX2022016453A (en) | 2020-06-24 | 2023-02-01 | Genentech Inc | Apoptosis resistant cell lines. |
WO2022002880A1 (en) | 2020-06-29 | 2022-01-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-protein s single-domain antibodies and polypeptides comprising thereof |
WO2022016037A1 (en) | 2020-07-17 | 2022-01-20 | Genentech, Inc. | Anti-notch2 antibodies and methods of use |
GB2597532A (en) | 2020-07-28 | 2022-02-02 | Femtogenix Ltd | Cytotoxic compounds |
EP4188550A1 (en) | 2020-07-29 | 2023-06-07 | Dynamicure Biotechnology LLC | Anti-cd93 constructs and uses thereof |
EP4189121A1 (en) | 2020-08-03 | 2023-06-07 | Genentech, Inc. | Diagnostic and therapeutic methods for lymphoma |
JP2023537761A (en) | 2020-08-14 | 2023-09-05 | エイシー イミューン ソシエテ アノニム | Humanized anti-TDP-43 binding molecules and uses thereof |
KR20230051677A (en) | 2020-08-20 | 2023-04-18 | 에이투 바이오쎄라퓨틱스, 인크. | Compositions and methods for treating mesothelin-positive cancer |
JP2023538115A (en) | 2020-08-20 | 2023-09-06 | エー2 バイオセラピューティクス, インコーポレイテッド | Compositions and methods for treating CEACAM-positive cancers |
WO2022040470A1 (en) * | 2020-08-20 | 2022-02-24 | A2 Biotherapeutics, Inc. | Compositions and methods for treating ceacam positive cancers |
WO2022043517A2 (en) | 2020-08-27 | 2022-03-03 | Cureab Gmbh | Anti-golph2 antibodies for macrophage and dendritic cell differentiation |
KR20230056766A (en) | 2020-08-28 | 2023-04-27 | 제넨테크, 인크. | CRISPR/Cas9 multiple knockout of host cell proteins |
EP4208201A1 (en) | 2020-09-04 | 2023-07-12 | F. Hoffmann-La Roche AG | Antibody that binds to vegf-a and ang2 and methods of use |
EP4225443A1 (en) | 2020-10-05 | 2023-08-16 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
EP4229082A1 (en) | 2020-10-16 | 2023-08-23 | AC Immune SA | Antibodies binding to alpha-synuclein for therapy and diagnosis |
AU2021366287A1 (en) | 2020-10-20 | 2023-04-13 | Kantonsspital St. Gallen | Antibodies or antigen-binding fragments specifically binding to Gremlin-1 and uses thereof |
WO2022093981A1 (en) | 2020-10-28 | 2022-05-05 | Genentech, Inc. | Combination therapy comprising ptpn22 inhibitors and pd-l1 binding antagonists |
CA3196076A1 (en) | 2020-11-04 | 2022-05-12 | Chi-Chung Li | Subcutaneous dosing of anti-cd20/anti-cd3 bispecific antibodies |
MX2023005131A (en) | 2020-11-04 | 2023-05-25 | Genentech Inc | Dosing for treatment with anti-cd20/anti-cd3 bispecific antibodies and anti-cd79b antibody drug conjugates. |
US20220162329A1 (en) | 2020-11-04 | 2022-05-26 | Genentech, Inc. | Dosing for treatment with anti-cd20/anti-cd3 bispecific antibodies |
US20220213199A1 (en) | 2020-12-17 | 2022-07-07 | Hoffmann-La Roche Inc. | Anti-HLA-G antibodies and use thereof |
WO2022140797A1 (en) | 2020-12-23 | 2022-06-30 | Immunowake Inc. | Immunocytokines and uses thereof |
KR20230124959A (en) | 2020-12-23 | 2023-08-28 | 이노벤트 바이오로직스 (쑤저우) 컴퍼니, 리미티드 | Anti-B7-H3 Antibodies and Uses Thereof |
AU2022206061A1 (en) | 2021-01-06 | 2023-07-06 | F. Hoffmann-La Roche Ag | Combination therapy employing a pd1-lag3 bispecific antibody and a cd20 t cell bispecific antibody |
JP2024504372A (en) | 2021-01-22 | 2024-01-31 | エルピス・バイオファーマシューティカルズ | Anti-PD-L1 monoclonal antibody and fusion protein with interleukin 15 (IL-15), interleukin 15 receptor 15alpha or interleukin 2 |
EP4284422A1 (en) | 2021-01-28 | 2023-12-06 | Vaccinvent GmbH | Method and means for modulating b-cell mediated immune responses |
WO2022162203A1 (en) | 2021-01-28 | 2022-08-04 | Vaccinvent Gmbh | Method and means for modulating b-cell mediated immune responses |
CN117120084A (en) | 2021-01-28 | 2023-11-24 | 维肯芬特有限责任公司 | Methods and means for modulating B cell mediated immune responses |
JP2024509695A (en) | 2021-02-03 | 2024-03-05 | ジェネンテック, インコーポレイテッド | Multispecific binding proteolysis platform and methods of use |
WO2022177963A1 (en) | 2021-02-17 | 2022-08-25 | Prometheus Biosciences, Inc. | Anti-cd30l antibodies and uses thereof |
CA3210069A1 (en) | 2021-03-03 | 2022-09-09 | Tong Zhu | Antibody-drug conjugates comprising an anti-bcma antibody |
TW202302646A (en) | 2021-03-05 | 2023-01-16 | 美商當康生物科技有限公司 | Anti-vista constructs and uses thereof |
AU2022232951A1 (en) | 2021-03-10 | 2023-10-19 | Immunowake Inc. | Immunomodulatory molecules and uses thereof |
AR125074A1 (en) | 2021-03-12 | 2023-06-07 | Genentech Inc | ANTI-KLK7 ANTIBODIES, ANTI-KLK5 ANTIBODIES, ANTI-KLK5/KLK7 MULTI-SPECIFIC ANTIBODIES AND METHODS OF USE |
KR20230156373A (en) | 2021-03-15 | 2023-11-14 | 제넨테크, 인크. | Therapeutic compositions and methods of treating lupus nephritis |
WO2022197877A1 (en) | 2021-03-19 | 2022-09-22 | Genentech, Inc. | Methods and compositions for time delayed bio-orthogonal release of cytotoxic agents |
EP4314049A1 (en) | 2021-03-25 | 2024-02-07 | Dynamicure Biotechnology LLC | Anti-igfbp7 constructs and uses thereof |
CA3215965A1 (en) | 2021-04-19 | 2022-10-27 | Amy Shen | Modified mammalian cells |
WO2022241446A1 (en) | 2021-05-12 | 2022-11-17 | Genentech, Inc. | Methods of using anti-cd79b immunoconjugates to treat diffuse large b-cell lymphoma |
EP4337317A1 (en) | 2021-05-14 | 2024-03-20 | Genentech, Inc. | Agonists of trem2 |
US20230115257A1 (en) | 2021-05-17 | 2023-04-13 | Curia Ip Holdings, Llc | Sars-cov-2 spike protein antibodies |
US20220372114A1 (en) | 2021-05-17 | 2022-11-24 | Curia Ip Holdings, Llc | Sars-cov-2 spike protein antibodies |
WO2022243261A1 (en) | 2021-05-19 | 2022-11-24 | F. Hoffmann-La Roche Ag | Agonistic cd40 antigen binding molecules targeting cea |
CN117396599A (en) | 2021-05-21 | 2024-01-12 | 基因泰克公司 | Modified cells for production of recombinant products of interest |
EP4355785A1 (en) | 2021-06-17 | 2024-04-24 | Amberstone Biosciences, Inc. | Anti-cd3 constructs and uses thereof |
AU2022302170A1 (en) | 2021-07-02 | 2023-12-21 | F. Hoffmann-La Roche Ag | Methods and compositions for treating cancer |
EP4370545A1 (en) | 2021-07-12 | 2024-05-22 | Genentech, Inc. | Structures for reducing antibody-lipase binding |
WO2023288241A1 (en) | 2021-07-14 | 2023-01-19 | Genentech, Inc. | Anti-c-c motif chemokine receptor 8 (ccr8) antibodies and methods of use |
WO2023004386A1 (en) | 2021-07-22 | 2023-01-26 | Genentech, Inc. | Brain targeting compositions and methods of use thereof |
KR20240036570A (en) | 2021-07-22 | 2024-03-20 | 에프. 호프만-라 로슈 아게 | Heterodimeric Fc domain antibodies |
WO2023010095A1 (en) | 2021-07-28 | 2023-02-02 | F. Hoffmann-La Roche Ag | Methods and compositions for treating cancer |
CA3226281A1 (en) | 2021-07-30 | 2023-02-02 | ONA Therapeutics S.L. | Anti-cd36 antibodies and their use to treat cancer |
WO2023011338A1 (en) | 2021-08-02 | 2023-02-09 | 信达生物制药(苏州)有限公司 | Anti-cd79b×cd3 bispecific antibody and use thereof |
WO2023012147A1 (en) | 2021-08-03 | 2023-02-09 | F. Hoffmann-La Roche Ag | Bispecific antibodies and methods of use |
US20230099756A1 (en) | 2021-08-07 | 2023-03-30 | Genentech, Inc. | Methods of using anti-cd79b immunoconjugates to treat diffuse large b-cell lymphoma |
EP4384553A1 (en) | 2021-08-13 | 2024-06-19 | Genentech, Inc. | Dosing for anti-tryptase antibodies |
EP4388014A1 (en) | 2021-08-19 | 2024-06-26 | F. Hoffmann-La Roche AG | Multivalent anti-variant fc-region antibodies and methods of use |
TW202328177A (en) | 2021-08-27 | 2023-07-16 | 美商建南德克公司 | Methods of treating tau pathologies |
WO2023034750A1 (en) | 2021-08-30 | 2023-03-09 | Genentech, Inc. | Anti-polyubiquitin multispecific antibodies |
WO2023043124A1 (en) * | 2021-09-17 | 2023-03-23 | 고려대학교 산학협력단 | GLYCATED FC VARIANTS WITH IMPROVED BINDING AFFINITY FOR FCγRIIIA |
WO2023043123A1 (en) * | 2021-09-17 | 2023-03-23 | 고려대학교 산학협력단 | Glycosylated fc variants with improved selective binding affinity to fcγriiia |
JPWO2023053282A1 (en) | 2021-09-29 | 2023-04-06 | ||
WO2023056069A1 (en) | 2021-09-30 | 2023-04-06 | Angiex, Inc. | Degrader-antibody conjugates and methods of using same |
WO2023056403A1 (en) | 2021-09-30 | 2023-04-06 | Genentech, Inc. | Methods for treatment of hematologic cancers using anti-tigit antibodies, anti-cd38 antibodies, and pd-1 axis binding antagonists |
WO2023058723A1 (en) | 2021-10-08 | 2023-04-13 | 中外製薬株式会社 | Method for preparing prefilled syringe formulation |
CA3236417A1 (en) | 2021-11-05 | 2023-05-11 | American Diagnostics & Therapy, Llc (Adxrx) | Monoclonal antibodies against carcinoembryonic antigens, and their uses |
WO2023086807A1 (en) | 2021-11-10 | 2023-05-19 | Genentech, Inc. | Anti-interleukin-33 antibodies and uses thereof |
AU2022389969A1 (en) | 2021-11-16 | 2024-05-02 | Genentech, Inc. | Methods and compositions for treating systemic lupus erythematosus (sle) with mosunetuzumab |
AR127692A1 (en) | 2021-11-16 | 2024-02-21 | Ac Immune Sa | ANTI-ASC ANTIBODIES FOR USE IN ANTI-INFLAMMATORY TREATMENTS |
WO2023114829A1 (en) | 2021-12-15 | 2023-06-22 | Genentech, Inc. | Stabilized il-18 polypeptides and uses thereof |
CA3240585A1 (en) | 2021-12-17 | 2023-06-22 | Wenfeng Xu | Anti-ox40 antibodies, multispecific antibodies and methods of use |
CA3240565A1 (en) | 2021-12-17 | 2023-06-22 | Wenfeng Xu | Anti-ox40 antibodies and methods of use |
AR128031A1 (en) | 2021-12-20 | 2024-03-20 | Hoffmann La Roche | ANTI-LTBR AGONIST ANTIBODIES AND BISPECIFIC ANTIBODIES THAT COMPRISE THEM |
AR128222A1 (en) | 2022-01-07 | 2024-04-10 | Johnson & Johnson Entpr Innovation Inc | IL-1b BINDING PROTEIN MATERIALS AND METHODS |
US20230322958A1 (en) | 2022-01-19 | 2023-10-12 | Genentech, Inc. | Anti-Notch2 Antibodies and Conjugates and Methods of Use |
AR128540A1 (en) | 2022-02-16 | 2024-05-22 | Ac Immune Sa | HUMANIZED ANTI-TDP-43 BINDING MOLECULES AND USES THEREOF |
US20230303719A1 (en) | 2022-03-03 | 2023-09-28 | Yale University | Humanized 3e10 antibodies, variants, and antigen binding fragments thereof |
WO2023173026A1 (en) | 2022-03-10 | 2023-09-14 | Sorrento Therapeutics, Inc. | Antibody-drug conjugates and uses thereof |
WO2023178357A1 (en) | 2022-03-18 | 2023-09-21 | Evolveimmune Therapeutics, Inc. | Bispecific antibody fusion molecules and methods of use thereof |
WO2023186756A1 (en) | 2022-03-28 | 2023-10-05 | F. Hoffmann-La Roche Ag | Interferon gamma variants and antigen binding molecules comprising these |
WO2023191816A1 (en) | 2022-04-01 | 2023-10-05 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2023194565A1 (en) | 2022-04-08 | 2023-10-12 | Ac Immune Sa | Anti-tdp-43 binding molecules |
US20230406930A1 (en) | 2022-04-13 | 2023-12-21 | Genentech, Inc. | Pharmaceutical compositions of therapeutic proteins and methods of use |
WO2023203177A1 (en) | 2022-04-20 | 2023-10-26 | Kantonsspital St. Gallen | Antibodies or antigen-binding fragments pan-specifically binding to gremlin-1 and gremlin-2 and uses thereof |
WO2023215737A1 (en) | 2022-05-03 | 2023-11-09 | Genentech, Inc. | Anti-ly6e antibodies, immunoconjugates, and uses thereof |
WO2023220597A1 (en) | 2022-05-10 | 2023-11-16 | Elpis Biopharmaceuticals | Engineered interleukin-2 receptor beta reduced-binding agonist |
WO2023219613A1 (en) | 2022-05-11 | 2023-11-16 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
TW202402810A (en) | 2022-05-11 | 2024-01-16 | 瑞士商赫孚孟拉羅股份公司 | Antibody that binds to vegf-a and il6 and methods of use |
WO2023240058A2 (en) | 2022-06-07 | 2023-12-14 | Genentech, Inc. | Prognostic and therapeutic methods for cancer |
WO2023237706A2 (en) | 2022-06-08 | 2023-12-14 | Institute For Research In Biomedicine (Irb) | Cross-specific antibodies, uses and methods for discovery thereof |
WO2023239803A1 (en) | 2022-06-08 | 2023-12-14 | Angiex, Inc. | Anti-tm4sf1 antibody-drug conjugates comprising cleavable linkers and methods of using same |
WO2023237928A2 (en) | 2022-06-10 | 2023-12-14 | Horizon Therapeutics Ireland Dac | Igf1r antibodies |
WO2024015897A1 (en) | 2022-07-13 | 2024-01-18 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2024020432A1 (en) | 2022-07-19 | 2024-01-25 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2024020564A1 (en) | 2022-07-22 | 2024-01-25 | Genentech, Inc. | Anti-steap1 antigen-binding molecules and uses thereof |
WO2024028731A1 (en) | 2022-08-05 | 2024-02-08 | Janssen Biotech, Inc. | Transferrin receptor binding proteins for treating brain tumors |
WO2024028732A1 (en) | 2022-08-05 | 2024-02-08 | Janssen Biotech, Inc. | Cd98 binding constructs for treating brain tumors |
WO2024037633A2 (en) | 2022-08-19 | 2024-02-22 | Evive Biotechnology (Shanghai) Ltd | Formulations comprising g-csf and uses thereof |
WO2024049949A1 (en) | 2022-09-01 | 2024-03-07 | Genentech, Inc. | Therapeutic and diagnostic methods for bladder cancer |
WO2024054929A1 (en) | 2022-09-07 | 2024-03-14 | Dynamicure Biotechnology Llc | Anti-vista constructs and uses thereof |
WO2024056668A1 (en) | 2022-09-12 | 2024-03-21 | Institut National de la Santé et de la Recherche Médicale | New anti-itgb8 antibodies and its uses thereof |
WO2024077239A1 (en) | 2022-10-07 | 2024-04-11 | Genentech, Inc. | Methods of treating cancer with anti-c-c motif chemokine receptor 8 (ccr8) antibodies |
WO2024092038A2 (en) | 2022-10-25 | 2024-05-02 | Ablexis, Llc | Anti-cd3 antibodies |
WO2024091991A1 (en) | 2022-10-25 | 2024-05-02 | Genentech, Inc. | Therapeutic and diagnostic methods for multiple myeloma |
WO2024094741A1 (en) | 2022-11-03 | 2024-05-10 | F. Hoffmann-La Roche Ag | Combination therapy with anti-cd19/anti-cd28 bispecific antibody |
WO2024102734A1 (en) | 2022-11-08 | 2024-05-16 | Genentech, Inc. | Compositions and methods of treating childhood onset idiopathic nephrotic syndrome |
WO2024107731A2 (en) | 2022-11-14 | 2024-05-23 | Ablexis, Llc | Anti-pd-l1 antibodies |
US20240190978A1 (en) | 2022-11-15 | 2024-06-13 | CSBioAsset LLC | Compositions and methods for immunomodulatory bifunctional fusion molecules |
WO2024108053A1 (en) | 2022-11-17 | 2024-05-23 | Sanofi | Ceacam5 antibody-drug conjugates and methods of use thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5624821A (en) | 1987-03-18 | 1997-04-29 | Scotgen Biopharmaceuticals Incorporated | Antibodies with altered effector functions |
WO1998023289A1 (en) | 1996-11-27 | 1998-06-04 | The General Hospital Corporation | MODULATION OF IgG BINDING TO FcRn |
WO1999051642A1 (en) | 1998-04-02 | 1999-10-14 | Genentech, Inc. | Antibody variants and fragments thereof |
Family Cites Families (77)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
USRE30985E (en) | 1978-01-01 | 1982-06-29 | Serum-free cell culture media | |
FR2413974A1 (en) | 1978-01-06 | 1979-08-03 | David Bernard | DRYER FOR SCREEN-PRINTED SHEETS |
US4275149A (en) | 1978-11-24 | 1981-06-23 | Syva Company | Macromolecular environment control in specific receptor assays |
US4318980A (en) | 1978-04-10 | 1982-03-09 | Miles Laboratories, Inc. | Heterogenous specific binding assay employing a cycling reactant as label |
US4419446A (en) | 1980-12-31 | 1983-12-06 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant DNA process utilizing a papilloma virus DNA as a vector |
NZ201705A (en) | 1981-08-31 | 1986-03-14 | Genentech Inc | Recombinant dna method for production of hepatitis b surface antigen in yeast |
US4601978A (en) | 1982-11-24 | 1986-07-22 | The Regents Of The University Of California | Mammalian metallothionein promoter system |
US4560655A (en) | 1982-12-16 | 1985-12-24 | Immunex Corporation | Serum-free cell culture medium and process for making same |
US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
US4490473A (en) * | 1983-03-28 | 1984-12-25 | Panab | Labeled antibodies and methods |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
DD266710A3 (en) | 1983-06-06 | 1989-04-12 | Ve Forschungszentrum Biotechnologie | Process for the biotechnical production of alkaline phosphatase |
US4752601A (en) * | 1983-08-12 | 1988-06-21 | Immunetech Pharmaceuticals | Method of blocking immune complex binding to immunoglobulin FC receptors |
US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
US4965199A (en) | 1984-04-20 | 1990-10-23 | Genentech, Inc. | Preparation of functional human factor VIII in mammalian cells using methotrexate based selection |
US4879231A (en) | 1984-10-30 | 1989-11-07 | Phillips Petroleum Company | Transformation of yeasts of the genus pichia |
US4737456A (en) | 1985-05-09 | 1988-04-12 | Syntex (U.S.A.) Inc. | Reducing interference in ligand-receptor binding assays |
GB8516415D0 (en) | 1985-06-28 | 1985-07-31 | Celltech Ltd | Culture of animal cells |
US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
US5091178A (en) | 1986-02-21 | 1992-02-25 | Oncogen | Tumor therapy with biologically active anti-tumor antibodies |
US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
GB8610600D0 (en) | 1986-04-30 | 1986-06-04 | Novo Industri As | Transformation of trichoderma |
US5985599A (en) * | 1986-05-29 | 1999-11-16 | The Austin Research Institute | FC receptor for immunoglobulin |
US5204244A (en) * | 1987-10-27 | 1993-04-20 | Oncogen | Production of chimeric antibodies by homologous recombination |
US5576184A (en) * | 1988-09-06 | 1996-11-19 | Xoma Corporation | Production of chimeric mouse-human antibodies with specificity to human tumor antigens |
ATE135397T1 (en) | 1988-09-23 | 1996-03-15 | Cetus Oncology Corp | CELL CULTIVATION MEDIUM FOR INCREASED CELL GROWTH, TO INCREASE THE LONGEVITY AND EXPRESSION OF THE PRODUCTS |
FR2646437B1 (en) | 1989-04-28 | 1991-08-30 | Transgene Sa | NOVEL DNA SEQUENCES, THEIR APPLICATION AS A SEQUENCE ENCODING A SIGNAL PEPTIDE FOR THE SECRETION OF MATURE PROTEINS BY RECOMBINANT YEASTS, EXPRESSION CASSETTES, PROCESSED YEASTS AND PROCESS FOR PREPARING THE SAME |
EP0402226A1 (en) | 1989-06-06 | 1990-12-12 | Institut National De La Recherche Agronomique | Transformation vectors for yeast yarrowia |
CA2062795A1 (en) | 1989-06-29 | 1990-12-30 | Michael W. Fanger | Bispecific reagents for aids therapy |
GB8916400D0 (en) * | 1989-07-18 | 1989-09-06 | Dynal As | Modified igg3 |
US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
US5364930A (en) * | 1990-10-16 | 1994-11-15 | Northwestern University | Synthetic C1q peptide fragments |
US5419904A (en) * | 1990-11-05 | 1995-05-30 | The Regents Of The University Of California | Human B-lymphoblastoid cell line secreting anti-ganglioside antibody |
WO1992020373A1 (en) | 1991-05-14 | 1992-11-26 | Repligen Corporation | Heteroconjugate antibodies for treatment of hiv infection |
US6136310A (en) * | 1991-07-25 | 2000-10-24 | Idec Pharmaceuticals Corporation | Recombinant anti-CD4 antibodies for human therapy |
WO1993008829A1 (en) | 1991-11-04 | 1993-05-13 | The Regents Of The University Of California | Compositions that mediate killing of hiv-infected cells |
GB9206422D0 (en) * | 1992-03-24 | 1992-05-06 | Bolt Sarah L | Antibody preparation |
AU4116793A (en) * | 1992-04-24 | 1993-11-29 | Board Of Regents, The University Of Texas System | Recombinant production of immunoglobulin-like domains in prokaryotic cells |
CA2140280A1 (en) | 1992-08-17 | 1994-03-03 | Avi J. Ashkenazi | Bispecific immunoadhesins |
US5736137A (en) | 1992-11-13 | 1998-04-07 | Idec Pharmaceuticals Corporation | Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma |
CA2149329C (en) | 1992-11-13 | 2008-07-15 | Darrell R. Anderson | Therapeutic application of chimeric and radiolabeled antibodies to human b lymphocyte restricted differentiation antigen for treatment of b cell lymphoma |
US6491916B1 (en) * | 1994-06-01 | 2002-12-10 | Tolerance Therapeutics, Inc. | Methods and materials for modulation of the immunosuppresive activity and toxicity of monoclonal antibodies |
US5885573A (en) * | 1993-06-01 | 1999-03-23 | Arch Development Corporation | Methods and materials for modulation of the immunosuppressive activity and toxicity of monoclonal antibodies |
WO1994029351A2 (en) | 1993-06-16 | 1994-12-22 | Celltech Limited | Antibodies |
US5731168A (en) * | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
US5730977A (en) * | 1995-08-21 | 1998-03-24 | Mitsui Toatsu Chemicals, Inc. | Anti-VEGF human monoclonal antibody |
US6750334B1 (en) | 1996-02-02 | 2004-06-15 | Repligen Corporation | CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor |
WO1997034631A1 (en) | 1996-03-18 | 1997-09-25 | Board Of Regents, The University Of Texas System | Immunoglobin-like domains with increased half lives |
US5834597A (en) | 1996-05-20 | 1998-11-10 | Protein Design Labs, Inc. | Mutated nonactivating IgG2 domains and anti CD3 antibodies incorporating the same |
US6277375B1 (en) * | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
DE19721700C1 (en) | 1997-05-23 | 1998-11-19 | Deutsches Krebsforsch | Mutant OKT3 antibody |
CA2293829C (en) * | 1997-06-24 | 2011-06-14 | Genentech, Inc. | Methods and compositions for galactosylated glycoproteins |
WO1999043713A1 (en) | 1998-02-25 | 1999-09-02 | Lexigen Pharmaceuticals Corporation | Enhancing the circulating half-life of antibody-based fusion proteins |
US6194551B1 (en) * | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
US6242195B1 (en) * | 1998-04-02 | 2001-06-05 | Genentech, Inc. | Methods for determining binding of an analyte to a receptor |
US6528624B1 (en) * | 1998-04-02 | 2003-03-04 | Genentech, Inc. | Polypeptide variants |
GB9809951D0 (en) | 1998-05-08 | 1998-07-08 | Univ Cambridge Tech | Binding molecules |
EP1105427A2 (en) | 1998-08-17 | 2001-06-13 | Abgenix, Inc. | Generation of modified molecules with increased serum half-lives |
US6737056B1 (en) * | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
PL220113B1 (en) | 1999-01-15 | 2015-08-31 | Genentech Inc | Variant of parent polypeptide comprising the Fc region, polypeptide comprising a variant of the Fc region with altered binding affinity of Fc gamma receptor (FcγR), a polypeptide comprising the variant of Fc region with altered binding affinity of neonatal Fc receptor (FcRn), a composition, isolated nucleic acid, vector, host cell, method for preparing the polypeptide variant, the use of the polypeptide variant and method for preparing a the Fc region variant |
US7183387B1 (en) * | 1999-01-15 | 2007-02-27 | Genentech, Inc. | Polypeptide variants with altered effector function |
US6676927B1 (en) * | 1999-01-20 | 2004-01-13 | The Rockefeller University | Animal model and methods for its use in the selection of cytotoxic antibodies |
ATE336514T1 (en) | 2000-02-11 | 2006-09-15 | Merck Patent Gmbh | INCREASE THE CIRCULATION HALF-LIFE OF ANTIBODIES-BASED FUSION PROTEINS |
JP2003531149A (en) * | 2000-04-13 | 2003-10-21 | ザ・ロツクフエラー・ユニバーシテイ | Enhancement of antibody-derived immune response |
ES2727425T3 (en) | 2000-12-12 | 2019-10-16 | Medimmune Llc | Molecules with prolonged half-lives, compositions and uses thereof |
US20040002587A1 (en) * | 2002-02-20 | 2004-01-01 | Watkins Jeffry D. | Fc region variants |
US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
EP1572091A4 (en) | 2002-07-09 | 2008-03-05 | Genentech Inc | Compositions and methods for the diagnosis and treatment of tumor |
CA2832136C (en) | 2002-09-27 | 2015-11-17 | Xencor | Optimized fc variants and methods for their generation |
EP1562972B1 (en) | 2002-10-15 | 2010-09-08 | Facet Biotech Corporation | ALTERATION OF FcRn BINDING AFFINITIES OR SERUM HALF-LIVES OF ANTIBODIES BY MUTAGENESIS |
US7217797B2 (en) | 2002-10-15 | 2007-05-15 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
US7608260B2 (en) * | 2003-01-06 | 2009-10-27 | Medimmune, Llc | Stabilized immunoglobulins |
CA2512729C (en) | 2003-01-09 | 2014-09-16 | Macrogenics, Inc. | Identification and engineering of antibodies with variant fc regions and methods of using same |
WO2005037867A1 (en) | 2003-10-15 | 2005-04-28 | Pdl Biopharma, Inc. | ALTERATION OF Fc-FUSION PROTEIN SERUM HALF-LIVES BY MUTAGENESIS OF POSITIONS 250, 314 AND/OR 428 OF THE HEAVY CHAIN CONSTANT REGION OF IG |
RU2367667C2 (en) * | 2004-08-19 | 2009-09-20 | Дженентек, Инк. | Polypeptide variants with changed effector function |
DOP2006000029A (en) * | 2005-02-07 | 2006-08-15 | Genentech Inc | ANTIBODY VARIANTS AND USES THEREOF. (VARIATIONS OF AN ANTIBODY AND USES OF THE SAME) |
-
2000
- 2000-01-14 PL PL394232A patent/PL220113B1/en unknown
- 2000-01-14 AU AU28505/00A patent/AU778683B2/en not_active Expired
- 2000-01-14 WO PCT/US2000/000973 patent/WO2000042072A2/en active Application Filing
- 2000-01-14 ES ES00906925.3T patent/ES2694002T3/en not_active Expired - Lifetime
- 2000-01-14 HU HU0104865A patent/HUP0104865A3/en unknown
- 2000-01-14 EP EP10185415A patent/EP2366713A3/en not_active Withdrawn
- 2000-01-14 KR KR1020067010091A patent/KR20060067983A/en not_active Application Discontinuation
- 2000-01-14 IL IL14405600A patent/IL144056A0/en unknown
- 2000-01-14 NZ NZ539776A patent/NZ539776A/en not_active IP Right Cessation
- 2000-01-14 KR KR1020087021958A patent/KR100940380B1/en active IP Right Grant
- 2000-01-14 KR KR1020017008932A patent/KR100887482B1/en active IP Right Grant
- 2000-01-14 EP EP10185306A patent/EP2364997A3/en not_active Withdrawn
- 2000-01-14 KR KR1020107006514A patent/KR101155191B1/en active IP Right Grant
- 2000-01-14 CN CN2005101067813A patent/CN1763097B/en not_active Expired - Lifetime
- 2000-01-14 PL PL388183A patent/PL209786B1/en unknown
- 2000-01-14 CA CA2359067A patent/CA2359067C/en not_active Expired - Lifetime
- 2000-01-14 BR BR0008758-0A patent/BR0008758A/en not_active Application Discontinuation
- 2000-01-14 HU HU1500355A patent/HU230769B1/en unknown
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- 2000-01-14 EP EP10185472A patent/EP2386574A3/en not_active Withdrawn
- 2000-01-14 MX MXPA04011973A patent/MX353234B/en unknown
- 2000-01-14 PL PL349770A patent/PL209392B1/en unknown
- 2000-01-14 JP JP2000593638A patent/JP2003512019A/en active Pending
- 2000-01-14 CN CNB00804905XA patent/CN1237076C/en not_active Expired - Lifetime
- 2000-01-14 EP EP00906925.3A patent/EP1141024B1/en not_active Expired - Lifetime
-
2001
- 2001-06-28 IL IL144056A patent/IL144056A/en not_active IP Right Cessation
- 2001-07-03 ZA ZA200105484A patent/ZA200105484B/en unknown
-
2006
- 2006-05-08 US US11/429,793 patent/US7371826B2/en not_active Expired - Lifetime
- 2006-05-08 US US11/429,792 patent/US20060194290A1/en not_active Abandoned
- 2006-09-22 HK HK06110619.4A patent/HK1090066A1/en not_active IP Right Cessation
-
2007
- 2007-11-16 US US11/941,750 patent/US7790858B2/en not_active Expired - Fee Related
-
2008
- 2008-02-19 US US12/033,642 patent/US7785791B2/en not_active Expired - Fee Related
- 2008-10-16 AU AU2008229968A patent/AU2008229968B2/en not_active Expired
-
2010
- 2010-06-08 JP JP2010131026A patent/JP5335735B2/en not_active Expired - Lifetime
-
2012
- 2012-09-27 IL IL222149A patent/IL222149B/en not_active IP Right Cessation
- 2012-11-15 IL IL223047A patent/IL223047A/en not_active IP Right Cessation
- 2012-11-15 IL IL223048A patent/IL223048A/en not_active IP Right Cessation
-
2013
- 2013-04-15 JP JP2013085174A patent/JP6230257B2/en not_active Expired - Lifetime
-
2016
- 2016-02-04 JP JP2016020011A patent/JP6312092B2/en not_active Expired - Lifetime
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5624821A (en) | 1987-03-18 | 1997-04-29 | Scotgen Biopharmaceuticals Incorporated | Antibodies with altered effector functions |
WO1998023289A1 (en) | 1996-11-27 | 1998-06-04 | The General Hospital Corporation | MODULATION OF IgG BINDING TO FcRn |
WO1999051642A1 (en) | 1998-04-02 | 1999-10-14 | Genentech, Inc. | Antibody variants and fragments thereof |
Non-Patent Citations (5)
Title |
---|
GHETIE ET AL., NATURE BIOTECHNOLOGY, vol. 15, 1997, pages 637 - 640 |
HENRY ET AL., BIOCHEMISTRY, vol. 36, 1997, pages 15568 - 15578 |
KABAT ET AL.: "Sequences of Proteins of Immunological Interest", 1991, NATIONAL INSTITUTES OF HEALTH |
MEDESAN ET AL., EUR J.LMMUNOL., vol. 28, 1998, pages 2092 - 2100 |
WARD; GHETIE, THERAPEUTIC IMMUNOLOGY, vol. 2, 1995, pages 77 - 94 |
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US8735545B2 (en) | 2003-03-03 | 2014-05-27 | Xencor, Inc. | Fc variants having increased affinity for fcyrllc |
US9663582B2 (en) | 2003-03-03 | 2017-05-30 | Xencor, Inc. | Optimized Fc variants |
US9657106B2 (en) | 2003-03-03 | 2017-05-23 | Xencor, Inc. | Optimized Fc variants |
US8084582B2 (en) | 2003-03-03 | 2011-12-27 | Xencor, Inc. | Optimized anti-CD20 monoclonal antibodies having Fc variants |
US10113001B2 (en) | 2003-03-03 | 2018-10-30 | Xencor, Inc. | Fc variants with increased affinity for FcyRIIc |
US10584176B2 (en) | 2003-03-03 | 2020-03-10 | Xencor, Inc. | Fc variants with increased affinity for FcγRIIc |
EP2062916A2 (en) | 2003-04-09 | 2009-05-27 | Genentech, Inc. | Therapy of autoimmune disease in a patient with an inadequate response to a TNF-Alpha inhibitor |
US7976838B2 (en) | 2003-04-09 | 2011-07-12 | Genentech, Inc. | Therapy of autoimmune disease in a patient with an inadequate response to a TNF-α inhibitor |
US7708994B2 (en) | 2003-04-09 | 2010-05-04 | Genentech, Inc. | Therapy of autoimmune disease in a patient with an inadequate response to a TNF-α inhibitor |
WO2004091657A2 (en) | 2003-04-09 | 2004-10-28 | Genentech, Inc. | Therapy of autoimmune disease in a patient with an inadequate response to a tnf-alpha inhibitor |
EP1620467A2 (en) * | 2003-05-02 | 2006-02-01 | Xencor, Inc. | Optimized fc variants and methods for their generation |
EP2368911A1 (en) | 2003-05-02 | 2011-09-28 | Xencor Inc. | Optimized Fc variants and methods for their generation |
EP3101030A1 (en) | 2003-05-02 | 2016-12-07 | Xencor, Inc. | Optimized fc variants and methods for their generation |
EP3838920A1 (en) | 2003-05-02 | 2021-06-23 | Xencor, Inc. | Optimized fc variants and methods for their generation |
AU2008261120B2 (en) * | 2003-05-02 | 2012-03-15 | Xencor, Inc | Optimized Fc variants and methods for their generation |
AU2004236160B2 (en) * | 2003-05-02 | 2008-10-23 | Xencor Inc. | Optimized Fc variants and methods for their generation |
US9051373B2 (en) | 2003-05-02 | 2015-06-09 | Xencor, Inc. | Optimized Fc variants |
US11168125B2 (en) | 2003-05-06 | 2021-11-09 | Bioverativ Therapeutics Inc. | Immunoglobulin chimeric monomer-dimer hybrids |
US8153125B2 (en) | 2003-05-20 | 2012-04-10 | Applied Molecular Evolution, Inc. | CD20 binding molecules |
EP2272868A2 (en) | 2003-06-05 | 2011-01-12 | Genentech, Inc. | Combination therapy for B cell disorders |
EP2292264A2 (en) | 2003-07-24 | 2011-03-09 | Innate Pharma | Methods and compositions for increasing the efficiency of therapeutic antibodies using NK cell potentiating compounds |
EP2420512A2 (en) | 2003-08-01 | 2012-02-22 | Genentech, Inc. | Anti-VEGF antibodies |
US8318917B2 (en) | 2003-08-22 | 2012-11-27 | Biogen Idec Ma Inc. | Nucleic acids encoding antibodies having altered effector function and methods for making the same |
US7863419B2 (en) | 2003-08-22 | 2011-01-04 | Biogen Idec Ma Inc. | Antibodies having altered effector function and methods for making the same |
US9714282B2 (en) | 2003-09-26 | 2017-07-25 | Xencor, Inc. | Optimized Fc variants and methods for their generation |
US7217798B2 (en) | 2003-10-15 | 2007-05-15 | Pdl Biopharma, Inc. | Alteration of Fc-fusion protein serum half-lives by mutagenesis |
WO2005040217A3 (en) * | 2003-10-17 | 2005-08-25 | Univ Cambridge Tech | Antibodies having a mutated amino acid residue at position 268 (ch2 region) in constant regions |
AU2004283135B2 (en) * | 2003-10-17 | 2008-08-14 | Cambridge University Technical Services Limited | Antibodies having a mutated amino acid residue at position 268 (CH2 region) in constant regions |
US9296820B2 (en) | 2003-11-05 | 2016-03-29 | Roche Glycart Ag | Polynucleotides encoding anti-CD20 antigen binding molecules with increased Fc receptor binding affinity and effector function |
US8883980B2 (en) | 2003-11-05 | 2014-11-11 | Roche Glycart Ag | Antigen binding molecules with increased Fc receptor binding affinity and effector function |
WO2005063815A2 (en) * | 2003-11-12 | 2005-07-14 | Biogen Idec Ma Inc. | Fcϝ receptor-binding polypeptide variants and methods related thereto |
WO2005063815A3 (en) * | 2003-11-12 | 2006-03-16 | Biogen Idec Inc | Fcϝ receptor-binding polypeptide variants and methods related thereto |
US8618252B2 (en) | 2003-11-12 | 2013-12-31 | Biogen Idec Ma Inc. | Neonatal Fc receptor (FcRn)-binding polypeptide variants, dimeric Fc binding proteins and methods related thereto |
EP1684790A2 (en) * | 2003-11-18 | 2006-08-02 | Iconic Therapeutics, Inc. | Homogeneous preparations of chimeric proteins |
EP1684790A4 (en) * | 2003-11-18 | 2008-04-30 | Iconic Therapeutics Inc | Homogeneous preparations of chimeric proteins |
US7930107B2 (en) | 2003-12-04 | 2011-04-19 | Xencor, Inc. | Methods of generating variant proteins with increased host string content |
EP2418220A2 (en) | 2003-12-10 | 2012-02-15 | Medarex, Inc. | Interferon alpha antibodies and their uses |
EP2865687A1 (en) | 2003-12-10 | 2015-04-29 | E. R. Squibb & Sons, L.L.C. | IP-10 antibodies and their uses |
EP2383295A1 (en) | 2003-12-10 | 2011-11-02 | Medarex, Inc. | IP-10 antibodies and their uses |
WO2005070963A1 (en) | 2004-01-12 | 2005-08-04 | Applied Molecular Evolution, Inc | Fc region variants |
EP3653641A1 (en) | 2004-02-19 | 2020-05-20 | Genentech, Inc. | Cdr-repaired antibodies |
US7521542B2 (en) | 2004-05-10 | 2009-04-21 | Macrogenics, Inc. | Humanized FcγRIIB-specific antibodies and methods of use thereof |
EP3130349A1 (en) | 2004-06-04 | 2017-02-15 | Genentech, Inc. | Method for treating multiple sclerosis |
EP2662390A1 (en) | 2004-06-21 | 2013-11-13 | Medarex, L.L.C. | Interferon alpha receptor 1 antibodies and their uses |
KR101357813B1 (en) | 2004-07-12 | 2014-02-06 | 마크로제닉스, 인크. | Identification and engineering of antibodies with variant fc regions and methods of using the same |
EP2940043A1 (en) * | 2004-07-15 | 2015-11-04 | Xencor, Inc. | Optimized fc variants |
CN103351434A (en) * | 2004-07-15 | 2013-10-16 | 赞科股份有限公司 | Optimized fc variants |
EP2471813A1 (en) | 2004-07-15 | 2012-07-04 | Xencor Inc. | Optimized Fc variants |
EP3342782A1 (en) | 2004-07-15 | 2018-07-04 | Xencor, Inc. | Optimized fc variants |
KR100863776B1 (en) * | 2004-07-15 | 2008-10-16 | 젠코어 인코포레이티드 | OPTIMIZED Fc VARIANTS |
CN103351434B (en) * | 2004-07-15 | 2015-09-30 | 赞科股份有限公司 | The Fc variant optimized |
EP3342782B1 (en) | 2004-07-15 | 2022-08-17 | Xencor, Inc. | Optimized fc variants |
WO2006019447A1 (en) * | 2004-07-15 | 2006-02-23 | Xencor, Inc. | Optimized fc variants |
US11820830B2 (en) | 2004-07-20 | 2023-11-21 | Xencor, Inc. | Optimized Fc variants |
US8961976B2 (en) | 2004-07-26 | 2015-02-24 | Biogen Idec Ma Inc. | Anti-CD154 antibodies |
US8647625B2 (en) | 2004-07-26 | 2014-02-11 | Biogen Idec Ma Inc. | Anti-CD154 antibodies |
US7740847B2 (en) | 2004-08-04 | 2010-06-22 | Applied Molecular Evolution, Inc. | Variant Fc regions |
EP1784424A2 (en) * | 2004-08-16 | 2007-05-16 | MedImmune, Inc. | Eph receptor fc variants with enhanced antibody dependent cell-mediated cytotoxicity activity |
EP1784424A4 (en) * | 2004-08-16 | 2009-03-18 | Medimmune Inc | Eph receptor fc variants with enhanced antibody dependent cell-mediated cytotoxicity activity |
US7659374B2 (en) | 2004-08-16 | 2010-02-09 | Medimmune, Llc | Eph receptor Fc variants with enhanced antibody dependent cell-mediated cytotoxicity activity |
WO2006031370A3 (en) * | 2004-08-19 | 2006-11-16 | Genentech Inc | Polypeptide variants with altered effector function |
WO2006031370A2 (en) * | 2004-08-19 | 2006-03-23 | Genentech, Inc. | Polypeptide variants with altered effector function |
WO2006041680A2 (en) | 2004-10-05 | 2006-04-20 | Genentech, Inc. | Method for treating vasculitis |
EP2371388A2 (en) | 2004-10-20 | 2011-10-05 | Genentech, Inc. | Antibody formulations |
EP3498294A1 (en) | 2004-10-20 | 2019-06-19 | Genentech, Inc. | Antibody formulations |
WO2006044908A2 (en) | 2004-10-20 | 2006-04-27 | Genentech, Inc. | Antibody formulation in histidine-acetate buffer |
EP1810035A4 (en) * | 2004-11-10 | 2010-03-17 | Macrogenics Inc | Engineering fc antibody regions to confer effector function |
US7632497B2 (en) | 2004-11-10 | 2009-12-15 | Macrogenics, Inc. | Engineering Fc Antibody regions to confer effector function |
EP1810035A2 (en) * | 2004-11-10 | 2007-07-25 | Magrogenics, Inc. | Engineering fc antibody regions to confer effector function |
AU2005335714B2 (en) * | 2004-11-10 | 2012-07-26 | Macrogenics, Inc. | Engineering Fc antibody regions to confer effector function |
US10336818B2 (en) | 2004-11-12 | 2019-07-02 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US9200079B2 (en) | 2004-11-12 | 2015-12-01 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US11198739B2 (en) | 2004-11-12 | 2021-12-14 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US8546543B2 (en) | 2004-11-12 | 2013-10-01 | Xencor, Inc. | Fc variants that extend antibody half-life |
US8883973B2 (en) | 2004-11-12 | 2014-11-11 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US8852586B2 (en) | 2004-11-12 | 2014-10-07 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US8318907B2 (en) | 2004-11-12 | 2012-11-27 | Xencor, Inc. | Fc variants with altered binding to FcRn |
CN102746404A (en) * | 2004-11-12 | 2012-10-24 | 赞科股份有限公司 | Fc variants with altered binding to fcrn |
US8802820B2 (en) | 2004-11-12 | 2014-08-12 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US9803023B2 (en) | 2004-11-12 | 2017-10-31 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US8367805B2 (en) | 2004-11-12 | 2013-02-05 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US8338574B2 (en) | 2004-11-12 | 2012-12-25 | Xencor, Inc. | FC variants with altered binding to FCRN |
WO2006073941A3 (en) * | 2004-12-31 | 2006-08-31 | Genentech Inc | Polypeptides that bind br3 and uses thereof |
WO2006073941A2 (en) * | 2004-12-31 | 2006-07-13 | Genentech, Inc. | Polypeptides that bind br3 and uses thereof |
EP3698807A1 (en) | 2005-01-21 | 2020-08-26 | Genentech, Inc. | Fixed dosing of her antibodies |
US8444973B2 (en) | 2005-02-15 | 2013-05-21 | Duke University | Anti-CD19 antibodies and uses in B cell disorders |
WO2006089133A2 (en) | 2005-02-15 | 2006-08-24 | Duke University | Anti-cd19 antibodies and uses in oncology |
EP2548575A1 (en) | 2005-02-15 | 2013-01-23 | Duke University | Anti-CD19 antibodies that mediate ADCC for use in treating autoimmune diseases |
US9260530B2 (en) | 2005-02-15 | 2016-02-16 | Duke University | Anti-CD19 antibodies and uses in B cell disorders |
EP2399605A1 (en) | 2005-02-23 | 2011-12-28 | Genentech, Inc. | Extending time to disease progression or survival in cancer patients |
EP3153525A1 (en) | 2005-03-23 | 2017-04-12 | Genmab A/S | Antibodies against cd38 for treatment of multiple myeloma |
EP2551282A2 (en) | 2005-03-23 | 2013-01-30 | Genmab A/S | Antibodies against CD38 for treatment of multiple myeloma |
EP2535355A2 (en) | 2005-03-23 | 2012-12-19 | Genmab A/S | Antibodies against CD38 for treatment of multiple myeloma |
EP3312196A1 (en) | 2005-03-23 | 2018-04-25 | Genmab A/S | Antibodies against cd38 for treatment of multiple myeloma |
EP2567976A2 (en) | 2005-03-23 | 2013-03-13 | Genmab A/S | Antibodies against CD38 for treatment of multiple myeloma |
WO2006105338A3 (en) * | 2005-03-31 | 2007-03-29 | Xencor Inc | Fc VARIANTS WITH OPTIMIZED PROPERTIES |
US9889197B2 (en) | 2005-04-15 | 2018-02-13 | Macrogenics, Inc. | Covalently-associated diabody complexes that possess charged coil domains and that are capable of enhanced binding to serum albumin |
US11254747B2 (en) | 2005-04-15 | 2022-02-22 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
US9296816B2 (en) | 2005-04-15 | 2016-03-29 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
US9963510B2 (en) | 2005-04-15 | 2018-05-08 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
US11254748B2 (en) | 2005-04-15 | 2022-02-22 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
US10093739B2 (en) | 2005-04-15 | 2018-10-09 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
US10093738B2 (en) | 2005-04-15 | 2018-10-09 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
EP3479844A1 (en) | 2005-04-15 | 2019-05-08 | MacroGenics, Inc. | Covalent diabodies and uses thereof |
EP2842968A1 (en) | 2005-04-29 | 2015-03-04 | Janssen Biotech, Inc. | Anti-IL-6 antibodies, compositions, methods and uses |
EP2221316A1 (en) | 2005-05-05 | 2010-08-25 | Duke University | Anti-CD19 antibody therapy for autoimmune disease |
EP2439272A2 (en) | 2005-05-09 | 2012-04-11 | Ono Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
EP3530736A2 (en) | 2005-05-09 | 2019-08-28 | ONO Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1 (pd-1) and methods for treating cancer using anti-pd-1 antibodies alone or in combination with other immunotherapeutics |
EP2439273A2 (en) | 2005-05-09 | 2012-04-11 | Ono Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
EP2161336A1 (en) | 2005-05-09 | 2010-03-10 | ONO Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
EP2418278A2 (en) | 2005-05-09 | 2012-02-15 | Ono Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
US7601335B2 (en) | 2005-05-20 | 2009-10-13 | Genentech, Inc. | Pretreatment of a biological sample from an autoimmune disease subject |
WO2007002543A2 (en) | 2005-06-23 | 2007-01-04 | Medimmune, Inc. | Antibody formulations having optimized aggregation and fragmentation profiles |
EP2452694A1 (en) | 2005-06-30 | 2012-05-16 | Janssen Biotech, Inc. | Anti-IL-23 antibodies, compositions, methods and uses |
EP3501537A1 (en) | 2005-06-30 | 2019-06-26 | Janssen Biotech, Inc. | Anti-il23 antibodies, compositions, methods and uses |
EP2982379A1 (en) | 2005-07-01 | 2016-02-10 | E. R. Squibb & Sons, L.L.C. | Human monoclonal antibodies to programmed death ligand 1 (pd-l1) |
US20100015644A1 (en) * | 2005-07-21 | 2010-01-21 | Genmab A/S | Potency assays for antibody drug substance binding to an fc receptor |
US9580506B2 (en) | 2005-07-21 | 2017-02-28 | Genmab A/S | Potency assays for antibody drug substance binding to an Fc receptor |
WO2007009469A3 (en) * | 2005-07-21 | 2007-04-12 | Genmab As | Potency assays for antibody drug substance binding to an fc receptor |
EP2295080A2 (en) | 2005-07-25 | 2011-03-16 | Trubion Pharmaceuticals, Inc. | B-cell reduction using CD37-specific and CD20-specific binding molecules |
EP2586798A2 (en) | 2005-07-25 | 2013-05-01 | Emergent Product Development Seattle, LLC | B-cell reduction using CD37-specific and CD20-specific binding molecules |
US10307481B2 (en) | 2005-07-25 | 2019-06-04 | Aptevo Research And Development Llc | CD37 immunotherapeutics and uses thereof |
EP2415483A1 (en) | 2005-07-25 | 2012-02-08 | Emergent Product Development Seattle, LLC | Single dose use of cd20-specific binding molecules |
EP2298815A1 (en) | 2005-07-25 | 2011-03-23 | Trubion Pharmaceuticals, Inc. | B-cell reduction using CD37-specific and CD20-specific binding molecules |
US10143748B2 (en) | 2005-07-25 | 2018-12-04 | Aptevo Research And Development Llc | B-cell reduction using CD37-specific and CD20-specific binding molecules |
US8697071B2 (en) | 2005-08-10 | 2014-04-15 | Macrogenics, Inc. | Identification and engineering of antibodies with variant Fc regions and methods of using same |
AU2006279945B2 (en) * | 2005-08-10 | 2012-04-12 | Macrogenics, Inc. | Identification and engineering of antibodies with variant FC regions and methods of using same |
EP1919503A2 (en) * | 2005-08-10 | 2008-05-14 | Magrogenics, Inc. | Identification and engineering of antibodies with variant fc regions and methods of using same |
EP2573114A1 (en) | 2005-08-10 | 2013-03-27 | MacroGenics, Inc. | Identification and engineering of antibodies with variant Fc regions and methods of using same |
EP1919503A4 (en) * | 2005-08-10 | 2010-11-17 | Macrogenics Inc | Identification and engineering of antibodies with variant fc regions and methods of using same |
EP2395023A2 (en) | 2005-08-26 | 2011-12-14 | GlycArt Biotechnology AG | Modified antigen binding molecules with altered cell signaling activity |
EP2395024A2 (en) | 2005-08-26 | 2011-12-14 | GlycArt Biotechnology AG | Modified antigen binding molecules with altered cell signaling activity |
WO2007041635A3 (en) * | 2005-10-03 | 2008-11-13 | Xencor Inc | Fc variants with optimized fc receptor binding properties |
AU2006299429B2 (en) * | 2005-10-03 | 2012-02-23 | Xencor, Inc. | Fc variants with optimized Fc receptor binding properties |
WO2007041635A2 (en) * | 2005-10-03 | 2007-04-12 | Xencor, Inc. | Fc variants with optimized fc receptor binding properties |
US9040041B2 (en) | 2005-10-03 | 2015-05-26 | Xencor, Inc. | Modified FC molecules |
US9574006B2 (en) | 2005-10-06 | 2017-02-21 | Xencor, Inc. | Optimized anti-CD30 antibodies |
WO2007044616A2 (en) | 2005-10-06 | 2007-04-19 | Xencor, Inc. | Optimized anti-cd30 antibodies |
US7973136B2 (en) | 2005-10-06 | 2011-07-05 | Xencor, Inc. | Optimized anti-CD30 antibodies |
EP2532679A1 (en) | 2005-10-21 | 2012-12-12 | Novartis AG | Human antibodies against il13 and therapeutic uses |
EP2532677A1 (en) | 2005-10-21 | 2012-12-12 | Novartis AG | Human antibodies against il13 and therapeutic uses |
US8753625B2 (en) | 2005-11-04 | 2014-06-17 | Genentech, Inc. | Use of complement inhibitors to treat ocular diseases |
WO2007055916A2 (en) | 2005-11-07 | 2007-05-18 | The Rockefeller University | Reagents, methods and systems for selecting a cytotoxic antibody or variant thereof |
EP2465870A1 (en) | 2005-11-07 | 2012-06-20 | Genentech, Inc. | Binding polypeptides with diversified and consensus VH/VL hypervariable sequences |
EP2455100A2 (en) | 2005-11-07 | 2012-05-23 | The Rockfeller University | Reagents, methods and systems for selecting a cytotoxic antibody or variant thereof |
US10654940B2 (en) | 2005-11-15 | 2020-05-19 | Genentech, Inc. | Method for treating joint damage |
US10450379B2 (en) | 2005-11-15 | 2019-10-22 | Genetech, Inc. | Method for treating joint damage |
US9726673B2 (en) | 2005-11-23 | 2017-08-08 | Genentech, Inc. | Methods and compositions related to B cell assays |
EP2623516A2 (en) | 2005-12-02 | 2013-08-07 | Genentech, Inc. | Compositions and methods for the treatment of diseases and disorders associated with cytokine signaling involving antibodies that bind to IL-22 and IL-22R |
EP3006466A2 (en) | 2005-12-02 | 2016-04-13 | Genentech, Inc. | Compositions and methods for the treatment of diseases and disorders associated with cytokine signaling involving antibodies that bind to il-22 and il-22r |
WO2007067992A2 (en) | 2005-12-08 | 2007-06-14 | Medarex, Inc. | Human monoclonal antibodies to fucosyl-gm1 and methods for using anti-fucosyl-gm1 |
US7981414B2 (en) | 2005-12-20 | 2011-07-19 | Cephalon Australia Pty Ltd | Anti-inflammatory dAb |
US8263076B2 (en) | 2005-12-20 | 2012-09-11 | Cephalon Australia Pty Ltd. | Anti-inflammatory dAb |
EP3760230A1 (en) | 2005-12-29 | 2021-01-06 | Janssen Biotech, Inc. | Human anti-il-23 antibodies, compositions, methods and uses |
EP3219328A1 (en) | 2005-12-29 | 2017-09-20 | Janssen Biotech, Inc. | Human anti-il-23 antibodies, compositions, method and uses |
EP2548577A1 (en) | 2005-12-29 | 2013-01-23 | Janssen Biotech, Inc. | Human anti-il-23 antibodies, compositions, methods and uses |
EP2402373A2 (en) | 2006-01-05 | 2012-01-04 | Genentech, Inc. | Anti-EphB4 Antibodies and Methods Using Same |
EP3156418A1 (en) | 2006-01-05 | 2017-04-19 | Genentech, Inc. | Anti-ephb4 antibodies and methods using same |
WO2007127506A2 (en) | 2006-01-20 | 2007-11-08 | Genentech, Inc. | Anti-ephrinb2 antibodies and methods using same |
US7846439B2 (en) | 2006-02-01 | 2010-12-07 | Cephalon Australia Pty Ltd | Domain antibody construct |
EP2540741A1 (en) | 2006-03-06 | 2013-01-02 | Aeres Biomedical Limited | Humanized anti-CD22 antibodies and their use in treatment of oncology, transplantation and autoimmune disease |
EP2468772A2 (en) | 2006-03-16 | 2012-06-27 | Genentech, Inc. | Antibodies to EGFL7 and methods for their use |
EP2366716A2 (en) | 2006-03-21 | 2011-09-21 | Genentech, Inc. | Combinatorial therapy involving alpha5beta1 antagonists |
US10934344B2 (en) | 2006-03-31 | 2021-03-02 | Chugai Seiyaku Kabushiki Kaisha | Methods of modifying antibodies for purification of bispecific antibodies |
US11046784B2 (en) | 2006-03-31 | 2021-06-29 | Chugai Seiyaku Kabushiki Kaisha | Methods for controlling blood pharmacokinetics of antibodies |
WO2007119796A1 (en) | 2006-04-14 | 2007-10-25 | Medical And Biological Laboratories Co., Ltd. | Mutant polypeptide having effector function |
EP2011870A4 (en) * | 2006-04-14 | 2010-09-15 | Medical & Biol Lab Co Ltd | Mutant polypeptide having effector function |
EP2011870A1 (en) * | 2006-04-14 | 2009-01-07 | Medical and Biological Laboratories Co., Ltd. | Mutant polypeptide having effector function |
EP2446904A2 (en) | 2006-05-30 | 2012-05-02 | Genentech, Inc. | Anti-CD22 antibodies, their immunoconjugates and uses thereof |
US8226945B2 (en) | 2006-05-30 | 2012-07-24 | Genentech, Inc. | Antibodies and immunoconjugates and uses therefor |
EP2447282A2 (en) | 2006-05-30 | 2012-05-02 | Genentech, Inc. | Anti-CD22 Antibodies, their Immunoconjugates and uses thereof |
US8968741B2 (en) | 2006-05-30 | 2015-03-03 | Genentech, Inc. | Anti-CD22 antibodies and immunoconjugates and methods of use |
US8524865B2 (en) | 2006-05-30 | 2013-09-03 | Genentech, Inc. | Antibodies and immunoconjugates and uses therefor |
US8394607B2 (en) | 2006-05-30 | 2013-03-12 | Genentech, Inc. | Anti-CD22 antibodies and immunoconjugates and methods of use |
US7803377B2 (en) | 2006-06-06 | 2010-09-28 | Genentech, Inc. | Anti-DLL4 antibodies and methods using same |
US8409577B2 (en) | 2006-06-12 | 2013-04-02 | Emergent Product Development Seattle, Llc | Single chain multivalent binding proteins with effector function |
US11098125B2 (en) | 2006-06-26 | 2021-08-24 | Macrogenics, Inc. | FcγRIIB-specific antibodies and methods of use thereof |
US9737599B2 (en) | 2006-06-26 | 2017-08-22 | Macrogenics, Inc. | Combination of FcγRIIB-specific antibodies and CD20-specific antibodies and methods of use thereof |
EP2505209A1 (en) | 2006-06-26 | 2012-10-03 | MacroGenics, Inc. | Fcgamma-RIIB-specific antibodies and methods of the use thereof |
US10100116B2 (en) | 2006-06-26 | 2018-10-16 | Macrogenics, Inc. | FcγRIIB-specific antibodies and methods of use thereof |
US8796439B2 (en) | 2006-07-14 | 2014-08-05 | Ac Immune S.A. | Nucleic acid molecules encoding a humanized antibody |
WO2008011081A2 (en) | 2006-07-19 | 2008-01-24 | The Trustees Of The University Of Pennsylvania | Wsx-1/p28 as a target for anti-inflammatory responses |
US11618788B2 (en) | 2006-08-14 | 2023-04-04 | Xencor, Inc. | Optimized antibodies that target CD19 |
US8524867B2 (en) | 2006-08-14 | 2013-09-03 | Xencor, Inc. | Optimized antibodies that target CD19 |
US9803020B2 (en) | 2006-08-14 | 2017-10-31 | Xencor, Inc. | Optimized antibodies that target CD19 |
US10626182B2 (en) | 2006-08-14 | 2020-04-21 | Xencor, Inc. | Optimized antibodies that target CD19 |
WO2008030611A2 (en) | 2006-09-05 | 2008-03-13 | Medarex, Inc. | Antibodies to bone morphogenic proteins and receptors therefor and methods for their use |
US8323653B2 (en) | 2006-09-08 | 2012-12-04 | Medimmune, Llc | Humanized anti-CD19 antibodies and their use in treatment of oncology, transplantation and autoimmune disease |
WO2008031056A2 (en) | 2006-09-08 | 2008-03-13 | Medimmune, Llc | Humanized anti-cd19 antibodies and their use in treatment of oncology, transplantation and autoimmune disease |
US8883992B2 (en) | 2006-09-08 | 2014-11-11 | Medimmune, Llc | Humanized anti-CD19 antibodies |
US9896505B2 (en) | 2006-09-08 | 2018-02-20 | Medimmune, Llc | Humanized anti-CD19 antibodies and their use in treatment of oncology, transplantation and autoimmune disease |
EP2845912A1 (en) | 2006-09-12 | 2015-03-11 | Genentech, Inc. | Methods and compositions for the diagnosis and treatment of lung cancer using KIT gene as genetic marker |
WO2008032833A1 (en) | 2006-09-14 | 2008-03-20 | Medical & Biological Laboratories Co., Ltd. | Antibody having enhanced adcc activity and method for production thereof |
US8394374B2 (en) | 2006-09-18 | 2013-03-12 | Xencor, Inc. | Optimized antibodies that target HM1.24 |
US9040042B2 (en) | 2006-09-18 | 2015-05-26 | Xencor, Inc. | Optimized antibodies that target HM1.24 |
EP2486941A1 (en) | 2006-10-02 | 2012-08-15 | Medarex, Inc. | Human antibodies that bind CXCR4 and uses thereof |
EP2407548A1 (en) * | 2006-10-16 | 2012-01-18 | MedImmune, LLC | Molecules with reduced half-lives, compositions and uses thereof |
EP2064335A2 (en) * | 2006-10-16 | 2009-06-03 | MedImmune, LLC | Molecules with reduced half-lives, compositions and uses thereof |
EP2064335A4 (en) * | 2006-10-16 | 2011-03-30 | Medimmune Llc | Molecules with reduced half-lives, compositions and uses thereof |
EP2829551A1 (en) | 2006-10-19 | 2015-01-28 | CSL Limited | High affinity antibody antagonists of interleukin-13 receptor alpha 1 |
EP2530090A2 (en) | 2006-10-19 | 2012-12-05 | CSL Limited | Anti-IL-13R alpha 1 antibodies and their uses thereof |
WO2008052187A2 (en) | 2006-10-27 | 2008-05-02 | Genentech. Inc. | Antibodies and immunoconjugates and uses therefor |
EP2845866A1 (en) | 2006-10-27 | 2015-03-11 | Genentech, Inc. | Antibodies and immunoconjugates and uses therefor |
US8618248B2 (en) | 2006-10-31 | 2013-12-31 | President And Fellows Of Harvard College | Phosphopeptide compositions and anti-phosphopeptide antibody compositions and methods of detecting phosphorylated peptides |
US8067002B2 (en) | 2006-11-02 | 2011-11-29 | Genentech, Inc. | Humanized anti-factor D antibodies |
WO2008076560A2 (en) | 2006-11-15 | 2008-06-26 | Medarex, Inc. | Human monoclonal antibodies to btla and methods of use |
WO2008070569A2 (en) | 2006-12-01 | 2008-06-12 | Medarex, Inc. | Human antibodies that bind cd22 and uses thereof |
US10711069B2 (en) | 2006-12-08 | 2020-07-14 | Macrogenics, Inc. | Methods for the treatment of disease using immunoglobulins having Fc regions with altered affinities for FcγRactivating and FcγRinhibiting |
US11787871B2 (en) | 2006-12-08 | 2023-10-17 | Macrogenics, Inc. | Methods for the treatment of disease using immunoglobulins having fc regions with altered affinities for FcgammaRactivating and FegammaRinhibiting |
US9708408B2 (en) | 2006-12-08 | 2017-07-18 | Macrogenics, Inc. | Methods for the treatment of disease using immunoglobulins having Fc Regions with altered affinities for FcγRactivating and FcγRinhibiting |
WO2009054863A2 (en) | 2006-12-13 | 2009-04-30 | Medarex, Inc. | Human antibodies that bind cd19 and uses thereof |
WO2008074004A2 (en) | 2006-12-14 | 2008-06-19 | Medarex, Inc. | Human antibodies that bind cd70 and uses thereof |
EP3095455A1 (en) | 2006-12-19 | 2016-11-23 | Genentech, Inc. | Vegf-specific antagonists for adjuvant and neoadjuvant therapy and the treatment of early stage tumors |
WO2008090960A1 (en) | 2007-01-24 | 2008-07-31 | Kyowa Hakko Kirin Co., Ltd. | Genetically recombinant antibody composition capable of binding specifically to ganglioside gm2 |
WO2008090959A1 (en) | 2007-01-24 | 2008-07-31 | Kyowa Hakko Kirin Co., Ltd. | Genetically recombinant antibody composition having enhanced effector activity |
EP2468776A2 (en) | 2007-02-09 | 2012-06-27 | Genentech, Inc. | Anti-Robo4 antibodies and uses therefor |
EP2899541A1 (en) | 2007-03-02 | 2015-07-29 | Genentech, Inc. | Predicting response to a HER dimerisation inhbitor based on low HER3 expression |
EP3199180A1 (en) | 2007-03-08 | 2017-08-02 | KaloBios Pharmaceuticals, Inc. | Epha3 antibodies for the treatment of solid tumors |
WO2008118324A2 (en) | 2007-03-26 | 2008-10-02 | Macrogenics, Inc. | Composition and method of treating cancer with an anti-uroplakin ib antibody |
EP3067368A1 (en) | 2007-04-27 | 2016-09-14 | Genentech, Inc. | Potent, stable and non-immunosuppressive anti-cd4 antibodies |
EP2599791A1 (en) | 2007-04-27 | 2013-06-05 | Genentech, Inc. | Potent, stable and non-immunosuppressive anti-CD4 antibodies |
EP2703011A2 (en) | 2007-05-07 | 2014-03-05 | MedImmune, LLC | Anti-icos antibodies and their use in treatment of oncology, transplantation and autoimmune disease |
EP2737907A2 (en) | 2007-05-07 | 2014-06-04 | MedImmune, LLC | Anti-icos antibodies and their use in treatment of oncology, transplantation and autoimmune disease |
WO2008141197A1 (en) * | 2007-05-10 | 2008-11-20 | Sea Lane Biotechnologies, Llc | Chain reaction creating oligomers from repeat units of binding molecules |
US8546539B2 (en) | 2007-05-14 | 2013-10-01 | Novimmune S.A. | Fc receptor-binding polypeptides with modified effector functions |
US9688755B2 (en) | 2007-05-14 | 2017-06-27 | Novimmune S.A. | Fc receptor-binding polypeptides with modified effector functions |
US10730931B2 (en) | 2007-06-01 | 2020-08-04 | Medimmune Limited | RSV-specific binding molecules and means for producing them |
US10059757B2 (en) | 2007-06-01 | 2018-08-28 | Medimmune Limited | RSV-specific binding molecules and means for producing them |
US9321831B2 (en) | 2007-06-01 | 2016-04-26 | Medimmune Limited | RSV-specific binding molecules and means for producing them |
WO2008150525A1 (en) | 2007-06-04 | 2008-12-11 | Genentech, Inc. | Anti-notch1 nrr antibodies and methods using same |
EP2592156A2 (en) | 2007-06-08 | 2013-05-15 | Genentech, Inc. | Gene expression markers of tumor resistance to HER2 inhibitor treatment |
US9585956B2 (en) | 2007-06-12 | 2017-03-07 | Ac Immune S.A. | Polynucleotides encoding anti-amyloid beta monoclonal antibodies |
US9175094B2 (en) | 2007-06-12 | 2015-11-03 | Ac Immune S.A. | Monoclonal antibody |
US8613923B2 (en) | 2007-06-12 | 2013-12-24 | Ac Immune S.A. | Monoclonal antibody |
US9146244B2 (en) | 2007-06-12 | 2015-09-29 | Ac Immune S.A. | Polynucleotides encoding an anti-beta-amyloid monoclonal antibody |
EP3424951A1 (en) | 2007-06-21 | 2019-01-09 | MacroGenics, Inc. | Covalent diabodies and uses thereof |
WO2008157379A2 (en) | 2007-06-21 | 2008-12-24 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
EP3327026A1 (en) | 2007-07-09 | 2018-05-30 | Genentech, Inc. | Prevention of disulfide bond reduction during recombinant production of polypeptides |
EP4335863A2 (en) | 2007-07-09 | 2024-03-13 | Genentech, Inc. | Prevention of disulfide bond reduction during recombinant production of polypeptides |
EP2586788A1 (en) | 2007-07-09 | 2013-05-01 | Genentech, Inc. | Prevention of disulfide bond reduction during recombinant production of polypeptides |
EP4219522A2 (en) | 2007-07-09 | 2023-08-02 | Genentech, Inc. | Prevention of disulfide bond reduction during recombinant production of polypeptides |
EP3597659A1 (en) | 2007-07-09 | 2020-01-22 | Genentech, Inc. | Prevention of disulfide bond reduction during recombinant production of polypeptides |
EP4245766A2 (en) | 2007-07-09 | 2023-09-20 | Genentech, Inc. | Prevention of disulfide bond reduction during recombinant production of polypeptides |
EP4365189A2 (en) | 2007-07-09 | 2024-05-08 | Genentech, Inc. | Prevention of disulfide bond reduction during recombinant production of polypeptides |
EP2078091A2 (en) * | 2007-07-10 | 2009-07-15 | Medimmune, LLC | CRYSTALS AND STRUCTURE OF HUMAN IgG Fc VARIANT |
EP2078091A4 (en) * | 2007-07-10 | 2010-09-01 | Medimmune Llc | CRYSTALS AND STRUCTURE OF HUMAN IgG Fc VARIANT |
EP2474557A2 (en) | 2007-07-16 | 2012-07-11 | Genentech, Inc. | Anti-CD79b antibodies and immunoconjugates and methods of use |
EP2502937A2 (en) | 2007-07-16 | 2012-09-26 | Genentech, Inc. | Anti-CD 79b Antibodies And Immunoconjugates And Methods Of Use |
EP2641618A2 (en) | 2007-07-16 | 2013-09-25 | Genentech, Inc. | Humanized anti-CD79B antibodies and immunoconjugates and methods of use |
EP2626371A1 (en) | 2007-07-31 | 2013-08-14 | MedImmune, LLC | Multispecific epitope binding proteins and uses thereof |
EP2769728A1 (en) | 2007-09-04 | 2014-08-27 | Compugen Ltd. | Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics |
EP2769729A1 (en) | 2007-09-04 | 2014-08-27 | Compugen Ltd. | Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics |
US10098934B2 (en) | 2007-09-04 | 2018-10-16 | Compugen Ltd | Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics |
WO2009032845A2 (en) | 2007-09-04 | 2009-03-12 | Compugen, Ltd. | Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics |
US11332533B2 (en) | 2007-09-26 | 2022-05-17 | Chugai Seiyaku Kabushiki Kaisha | Modified antibody constant region |
US9828429B2 (en) | 2007-09-26 | 2017-11-28 | Chugai Seiyaku Kabushiki Kaisha | Method of modifying isoelectric point of antibody via amino acid substitution in CDR |
US11248053B2 (en) | 2007-09-26 | 2022-02-15 | Chugai Seiyaku Kabushiki Kaisha | Method of modifying isoelectric point of antibody via amino acid substitution in CDR |
US9403902B2 (en) | 2007-10-05 | 2016-08-02 | Ac Immune S.A. | Methods of treating ocular disease associated with amyloid-beta-related pathology using an anti-amyloid-beta antibody |
EP2586796A1 (en) | 2007-10-12 | 2013-05-01 | Novartis AG | Compositions and methods for use for antibodies against sclerostin |
EP2233149A1 (en) | 2007-10-16 | 2010-09-29 | ZymoGenetics, Inc. | Combination of BLYS inhibition and anti-CD20 agents for treatment of autoimmune disease |
WO2009054435A1 (en) | 2007-10-24 | 2009-04-30 | Otsuka Chemical Co., Ltd. | Polypeptide having enhanced effector function |
US11932685B2 (en) | 2007-10-31 | 2024-03-19 | Xencor, Inc. | Fc variants with altered binding to FcRn |
EP3305324A1 (en) | 2007-11-02 | 2018-04-11 | Novartis AG | Molecules and methods for modulating low-density-lipoprotein receptor-related protein 6 (lrp6) |
EP2567709A2 (en) | 2007-11-02 | 2013-03-13 | Novartis AG | Molecules and methods for modulating low-density-lipoprotein receptor-related protein 6 (LRP6) |
EP3360567A1 (en) | 2007-11-07 | 2018-08-15 | Genentech, Inc. | Amp for use in treating microbial disorders |
EP2851372A1 (en) | 2007-11-30 | 2015-03-25 | Genentech, Inc. | Anti-VEGF antibodies |
EP3173425A1 (en) | 2007-11-30 | 2017-05-31 | Genentech, Inc. | Anti-vegf antibodies |
EP2769993A1 (en) | 2007-12-14 | 2014-08-27 | Novo Nordisk A/S | Antibodies against human NKG2D and uses thereof |
US8795667B2 (en) | 2007-12-19 | 2014-08-05 | Macrogenics, Inc. | Compositions for the prevention and treatment of smallpox |
EP2604628A2 (en) | 2007-12-21 | 2013-06-19 | Medimmune Limited | Binding members for interleukin-4 receptor alpha (IL-4R) - 173 |
WO2009081201A2 (en) | 2007-12-21 | 2009-07-02 | Medimmune Limited | BINDING MEMBERS FOR INTERLEUKIN-4 RECEPTOR ALPHA (IL-4Rα) - 173 |
EP3211010A1 (en) | 2007-12-21 | 2017-08-30 | Medimmune Limited | Binding members for interleukin-4 receptor alpha (il-4r) - 173 |
KR101616758B1 (en) | 2007-12-26 | 2016-04-29 | 젠코어 인코포레이티드 | Fc VARIANTS WITH ALTERED BINDING TO FcRn |
CN105418762A (en) * | 2007-12-26 | 2016-03-23 | Xencor公司 | Fc variants with altered binding to fcrn |
KR20100099179A (en) * | 2007-12-26 | 2010-09-10 | 젠코어 인코포레이티드 | Fc variants with altered binding to fcrn |
EP2077281A1 (en) | 2008-01-02 | 2009-07-08 | Bergen Teknologioverforing AS | Anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome |
US7914785B2 (en) | 2008-01-02 | 2011-03-29 | Bergen Teknologieverforing As | B-cell depleting agents, like anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome |
WO2009092011A1 (en) | 2008-01-18 | 2009-07-23 | Medimmune, Llc | Cysteine engineered antibodies for site-specific conjugation |
EP3401335A1 (en) | 2008-01-30 | 2018-11-14 | Genentech, Inc. | Composition comprising antibody that binds to domain ii of her2 and acidic variants thereof |
EP4119583A1 (en) | 2008-01-30 | 2023-01-18 | Genentech, Inc. | Composition comprising antibody that binds to domain ii of her2 and acidic variants thereof |
EP2657253A2 (en) | 2008-01-31 | 2013-10-30 | Genentech, Inc. | Anti-CD79b antibodies and immunoconjugates and methods of use |
US8039596B2 (en) | 2008-02-05 | 2011-10-18 | Bristol-Myers Squibb Company | Alpha 5-beta 1 antibodies and their uses |
EP2650017A2 (en) | 2008-02-05 | 2013-10-16 | Bristol-Myers Squibb Company | Alpha 5 - beta 1 antibodies and their uses |
EP2641612A1 (en) | 2008-02-05 | 2013-09-25 | Bristol-Myers Squibb Company | Alpha 5 - beta 1 antibodies and their uses |
US8399647B2 (en) | 2008-02-05 | 2013-03-19 | Pfizer Inc. | Alpha5-beta1 antibodies and their uses |
WO2009100309A2 (en) | 2008-02-08 | 2009-08-13 | Medimmune, Llc | Anti-ifnar1 antibodies with reduced fc ligand affinity |
US9695236B2 (en) | 2008-04-02 | 2017-07-04 | Macrogenics, Inc. | BCR-complex-specific antibodies and methods of using same |
EP3067063A1 (en) | 2008-04-02 | 2016-09-14 | MacroGenics, Inc. | Her2/neu-specific antibodies and methods of using same |
US10479831B2 (en) | 2008-04-02 | 2019-11-19 | Macrogenics, Inc | BCR-complex-specific antibodies and methods of using same |
EP3045475A1 (en) | 2008-04-02 | 2016-07-20 | MacroGenics, Inc. | Bcr-complex-specific antibodies and methods of using same |
WO2009151717A2 (en) | 2008-04-02 | 2009-12-17 | Macrogenics, Inc. | Bcr-complex-specific antibodies and methods of using same |
US10131713B2 (en) | 2008-04-02 | 2018-11-20 | Macrogenics, Inc. | HER2/neu-specific antibodies and methods of using same |
US11028183B2 (en) | 2008-04-02 | 2021-06-08 | Macrogenics, Inc. | HER2/neu-specific antibodies and methods of using same |
US11359194B2 (en) | 2008-04-11 | 2022-06-14 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding two or more antigen molecules repeatedly |
US10472623B2 (en) | 2008-04-11 | 2019-11-12 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding two or more antigen molecules repeatedly |
US11371039B2 (en) | 2008-04-11 | 2022-06-28 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly |
US9890377B2 (en) | 2008-04-11 | 2018-02-13 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly |
US9101609B2 (en) | 2008-04-11 | 2015-08-11 | Emergent Product Development Seattle, Llc | CD37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof |
US9868948B2 (en) | 2008-04-11 | 2018-01-16 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly |
US9676868B2 (en) | 2008-04-28 | 2017-06-13 | Genentech, Inc. | Humanized anti-factor D antibodies and uses thereof |
US8273352B2 (en) | 2008-04-28 | 2012-09-25 | Genentech, Inc. | Humanized anti-factor D antibodies and uses thereof |
EP3002295A1 (en) | 2008-04-28 | 2016-04-06 | Genentech, Inc. | Humanized anti-factor d antibodies and uses thereof |
WO2010033279A2 (en) | 2008-06-04 | 2010-03-25 | Macrogenics, Inc. | Antibodies with altered binding to fcrn and methods of using same |
EP2837388A1 (en) | 2008-08-05 | 2015-02-18 | Novartis AG | Compositions and methods for antibodies targeting complement protein C5 |
WO2010015608A1 (en) | 2008-08-05 | 2010-02-11 | Novartis Ag | Compositions and methods for antibodies targeting complement protein c5 |
EP2815766A1 (en) | 2008-08-05 | 2014-12-24 | Novartis AG | Compositions and methods for antibodies targeting complement protein C5 |
EP2905030A1 (en) | 2008-08-11 | 2015-08-12 | E. R. Squibb & Sons, L.L.C. | Human antibodies that bind lymphocyte activation gene-3 (LAG-3) and uses thereof |
EP3597216A1 (en) | 2008-08-11 | 2020-01-22 | E. R. Squibb & Sons, L.L.C. | Human antibodies that bind lymphocyte activation gene-3 (lag-3) and uses thereof |
EP4147714A1 (en) | 2008-08-11 | 2023-03-15 | E. R. Squibb & Sons, L.L.C. | Human antibodies that bind lymphocyte activation gene-3 (lag-3) and uses thereof |
US9683047B2 (en) | 2008-09-16 | 2017-06-20 | Genentech, Inc. | Methods for treating progressive multiple sclerosis |
EP4364800A2 (en) | 2008-09-16 | 2024-05-08 | F. Hoffmann-La Roche AG | Methods for treating progressive multiple sclerosis |
EP3747464A1 (en) | 2008-09-16 | 2020-12-09 | F. Hoffmann-La Roche AG | Methods for treating progessive multiple sclerosis using an anti-cd20 antibody |
US9994642B2 (en) | 2008-09-16 | 2018-06-12 | Genentech, Inc. | Methods for treating progressive multiple sclerosis |
EP3095463A2 (en) | 2008-09-16 | 2016-11-23 | F. Hoffmann-La Roche AG | Methods for treating progressive multiple sclerosis |
EP2927244A1 (en) | 2008-09-19 | 2015-10-07 | MedImmune, LLC | Antibodies directed to DLL4 and uses thereof |
WO2010045193A1 (en) * | 2008-10-14 | 2010-04-22 | Genentech, Inc. | Immunoglobulin variants and uses thereof |
EP3524620A1 (en) * | 2008-10-14 | 2019-08-14 | Genentech, Inc. | Immunoglobulin variants and uses thereof |
US8741604B2 (en) | 2008-11-07 | 2014-06-03 | Medimmune Limited | Nucleic acid molecule encoding a specific IL-1R1 antibody |
US8298533B2 (en) | 2008-11-07 | 2012-10-30 | Medimmune Limited | Antibodies to IL-1R1 |
US9200074B2 (en) | 2008-11-07 | 2015-12-01 | Medimmune Limited | Antibodies to IL-1 R1 and methods of making them |
WO2010056804A1 (en) | 2008-11-12 | 2010-05-20 | Medimmune, Llc | Antibody formulation |
EP3178478A1 (en) | 2008-11-22 | 2017-06-14 | F. Hoffmann-La Roche AG | Use of anti-vegf antibody in combination with chemotherapy for treating breast cancer |
EP2752189A1 (en) | 2008-11-22 | 2014-07-09 | F. Hoffmann-La Roche AG | Use of anti-vegf antibody in combination with chemotherapy for treating breast cancer |
WO2010067308A2 (en) | 2008-12-08 | 2010-06-17 | Compugen Ltd. | Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics |
EP2865689A1 (en) | 2008-12-08 | 2015-04-29 | Compugen Ltd. | FAM26F polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics |
US8775090B2 (en) | 2008-12-12 | 2014-07-08 | Medimmune, Llc | Crystals and structure of a human IgG Fc variant with enhanced FcRn binding |
EP3482769A1 (en) | 2008-12-19 | 2019-05-15 | MacroGenics, Inc. | Covalent diabodies and uses thereof |
WO2010080538A1 (en) | 2008-12-19 | 2010-07-15 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
EP2786762A2 (en) | 2008-12-19 | 2014-10-08 | MacroGenics, Inc. | Covalent diabodies and uses thereof |
WO2010075249A2 (en) | 2008-12-22 | 2010-07-01 | Genentech, Inc. | A method for treating rheumatoid arthritis with b-cell antagonists |
WO2010072740A2 (en) | 2008-12-23 | 2010-07-01 | Astrazeneca Ab | TARGETED BINDING AGENTS DIRECTED TO α5β1 AND USES THEREOF |
WO2010078526A1 (en) | 2008-12-31 | 2010-07-08 | Biogen Idec Ma Inc. | Anti-lymphotoxin antibodies |
US9879249B2 (en) | 2009-02-17 | 2018-01-30 | Redwood Bioscience, Inc. | Aldehyde-tagged protein-based drug carriers and methods of use |
US8679492B2 (en) | 2009-02-23 | 2014-03-25 | Glenmark Pharmaceuticals S.A. | Humanized antibodies that bind to CD19 and their uses |
WO2010102175A1 (en) | 2009-03-05 | 2010-09-10 | Medarex, Inc. | Fully human antibodies specific to cadm1 |
WO2010102244A1 (en) | 2009-03-06 | 2010-09-10 | Kalobios Pharmaceuticals, Inc. | Treatment of leukemias and chronic myeloproliferative diseases with antibodies to epha3 |
EP2433967A2 (en) | 2009-03-16 | 2012-03-28 | Cephalon Australia Pty Ltd | Humanised antibodies with anti-tumour activity |
US8470320B2 (en) | 2009-03-16 | 2013-06-25 | Cephalon Australia Pty. Ltd. | Humanised antibodies with anti-tumour activity |
US8901279B2 (en) | 2009-03-16 | 2014-12-02 | Teva Pharmaceuticals Australia Pty Ltd | Humanized antibodies with anti-tumor activity |
WO2010106180A2 (en) | 2009-03-20 | 2010-09-23 | Lfb Biotechnologies | Optimized fc variants |
EP3674318A1 (en) | 2009-03-20 | 2020-07-01 | Laboratoire Français du Fractionnement et des Biotechnologies | Optimized fc variants |
EP2233500A1 (en) | 2009-03-20 | 2010-09-29 | LFB Biotechnologies | Optimized Fc variants |
EP3395831A1 (en) | 2009-03-20 | 2018-10-31 | Laboratoire Français du Fractionnement et des Biotechnologies | Optimized fc variants |
USRE45992E1 (en) | 2009-03-20 | 2016-05-03 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Optimized FC variants |
EP2805969A3 (en) * | 2009-03-20 | 2016-03-30 | Laboratoire Français du Fractionnement et des Biotechnologies | Optimized FC variants |
US8742074B2 (en) | 2009-03-20 | 2014-06-03 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Optimized FC variants |
USRE46585E1 (en) | 2009-03-20 | 2017-10-24 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Optimized FC variants |
WO2010106180A3 (en) * | 2009-03-20 | 2010-12-09 | Lfb Biotechnologies | Optimized fc variants |
US20120142593A1 (en) * | 2009-03-24 | 2012-06-07 | Bayer Healthcare Llc | Factor VIII Variants and Methods of Use |
US8710189B2 (en) | 2009-03-25 | 2014-04-29 | Genentech, Inc. | Anti-FGFR3 antibodies and methods using same |
WO2010111254A1 (en) | 2009-03-25 | 2010-09-30 | Genentech, Inc. | Novel anti-alpha5beta1 antibodies and uses thereof |
WO2010111367A1 (en) | 2009-03-25 | 2010-09-30 | Genentech, Inc. | Anti-fgfr3 antibodies and methods using same |
US9499623B2 (en) | 2009-03-25 | 2016-11-22 | Genentech, Inc. | Anti-FGFR3 antibodies and methods using same |
EP2679600A1 (en) | 2009-03-25 | 2014-01-01 | Genentech, Inc. | Anti-FGFR3 antibodies and methods using same |
US9161977B2 (en) | 2009-03-25 | 2015-10-20 | F. Hoffmann-La Roche Ag | Anti-FGFR3 antibodies and methods using same |
US10000571B2 (en) | 2009-03-25 | 2018-06-19 | Genentech, Inc. | Anti-FGFR3 antibodies and methods using same |
US11401333B2 (en) | 2009-03-25 | 2022-08-02 | Genentech, Inc. | Anti-FGFR3 antibodies and methods using same |
US10287356B2 (en) | 2009-03-25 | 2019-05-14 | Genentech, Inc. | Anti-FGFR3 antibodies and methods using same |
US8410250B2 (en) | 2009-03-25 | 2013-04-02 | Genentech, Inc. | Anti-FGFR3 antibodies and methods using same |
WO2010112458A1 (en) | 2009-03-31 | 2010-10-07 | Novartis Ag | Composition and methods of use for therapeutic antibodies specific for the il-12 receptore betal subunit |
EP3009454A2 (en) | 2009-04-20 | 2016-04-20 | Oxford Bio Therapeutics Limited | Antibodies specific to cadherin-17 |
US9062116B2 (en) | 2009-04-23 | 2015-06-23 | Infinity Pharmaceuticals, Inc. | Anti-fatty acid amide hydrolase-2 antibodies and uses thereof |
EP3275900A1 (en) | 2009-04-27 | 2018-01-31 | Novartis AG | Compositions and methods for increasing muscle growth |
WO2010125003A1 (en) | 2009-04-27 | 2010-11-04 | Novartis Ag | Compositions and methods for increasing muscle growth |
WO2010146550A1 (en) | 2009-06-18 | 2010-12-23 | Pfizer Inc. | Anti notch-1 antibodies |
EP3431501A1 (en) | 2009-06-18 | 2019-01-23 | Pfizer Inc | Anti notch-1 antibodies |
US9090690B2 (en) | 2009-06-18 | 2015-07-28 | Pfizer Inc. | Anti Notch-1 antibodies |
EP2711018A1 (en) | 2009-06-22 | 2014-03-26 | MedImmune, LLC | Engineered Fc regions for site-specific conjugation |
WO2011008696A2 (en) | 2009-07-13 | 2011-01-20 | Genentech, Inc. | Diagnostic methods and compositions for treatment of cancer |
WO2011014457A1 (en) | 2009-07-27 | 2011-02-03 | Genentech, Inc. | Combination treatments |
WO2011014750A1 (en) | 2009-07-31 | 2011-02-03 | Genentech, Inc. | Inhibition of tumor metastasis using bv8- or g-csf-antagonists |
EP3199551A2 (en) | 2009-07-31 | 2017-08-02 | E. R. Squibb & Sons, L.L.C. | Fully human antibodies to btla |
WO2011014438A1 (en) | 2009-07-31 | 2011-02-03 | N.V. Organon | Fully human antibodies to btla |
WO2011019619A1 (en) | 2009-08-11 | 2011-02-17 | Genentech, Inc. | Production of proteins in glutamine-free cell culture media |
US10982003B2 (en) | 2009-08-11 | 2021-04-20 | Genentech, Inc. | Production of proteins in glutamine-free cell culture media |
US9714293B2 (en) | 2009-08-11 | 2017-07-25 | Genentech, Inc. | Production of proteins in glutamine-free cell culture media |
EP3760712A1 (en) | 2009-08-11 | 2021-01-06 | F. Hoffmann-La Roche AG | Production of proteins in glutamine-free cell culture media |
US8512983B2 (en) | 2009-08-11 | 2013-08-20 | Martin Gawlitzek | Production of proteins in glutamine-free cell culture media |
WO2011020049A1 (en) | 2009-08-14 | 2011-02-17 | Genentech, Inc. | Biological markers for monitoring patient response to vegf antagonists |
WO2011022264A1 (en) | 2009-08-15 | 2011-02-24 | Genentech, Inc. | Anti-angiogenesis therapy for the treatment of previously treated breast cancer |
EP3090758A1 (en) | 2009-08-15 | 2016-11-09 | F. Hoffmann-La Roche AG | Anti-angiogenesis therapy for the treatment of previously treated breast cancer |
WO2011021146A1 (en) | 2009-08-20 | 2011-02-24 | Pfizer Inc. | Osteopontin antibodies |
CN102596994A (en) * | 2009-08-21 | 2012-07-18 | 英国龙沙生物医药股份有限公司 | Variant immunoglobulins with improved manufacturability |
US9758776B2 (en) | 2009-08-24 | 2017-09-12 | Amunix Operating Inc. | Coagulation factor IX compositions and methods of making and using same |
US9376672B2 (en) | 2009-08-24 | 2016-06-28 | Amunix Operating Inc. | Coagulation factor IX compositions and methods of making and using same |
WO2011028950A1 (en) | 2009-09-02 | 2011-03-10 | Genentech, Inc. | Mutant smoothened and methods of using the same |
US11401348B2 (en) | 2009-09-02 | 2022-08-02 | Xencor, Inc. | Heterodimeric Fc variants |
EP3211094A2 (en) | 2009-09-03 | 2017-08-30 | F. Hoffmann-La Roche AG | Methods for treating, diagnosing, and monitoring rheumatoid arthritis |
WO2011029823A1 (en) | 2009-09-09 | 2011-03-17 | Novartis Ag | Monoclonal antibody reactive with cd63 when expressed at the surface of degranulated mast cells |
WO2011032013A1 (en) | 2009-09-11 | 2011-03-17 | Genentech, Inc. | Method to identify a patient with an increased likelihood of responding to an anti-cancer agent |
WO2011033006A1 (en) | 2009-09-17 | 2011-03-24 | F. Hoffmann-La Roche Ag | Methods and compositions for diagnostics use in cancer patients |
US10035843B2 (en) | 2009-10-06 | 2018-07-31 | Medimmune Limited | RSV-specific binding molecule |
US10723786B2 (en) | 2009-10-06 | 2020-07-28 | Medimmune, Limited | RSV-specific binding molecule |
WO2011044368A1 (en) | 2009-10-07 | 2011-04-14 | Macrogenics, Inc. | Fc region-containing polypeptides that exhibit improved effector function due to alterations of the extent of fucosylation, and methods for their use |
WO2011047083A1 (en) | 2009-10-13 | 2011-04-21 | Oxford Biotherapeutics Ltd. | Antibodies against epha10 |
WO2011053465A1 (en) | 2009-10-14 | 2011-05-05 | Kalobios Pharmaceuticals, Inc. | Antibodies to epha3 |
WO2011050188A1 (en) | 2009-10-22 | 2011-04-28 | Genentech, Inc. | Anti-hepsin antibodies and methods using same |
EP3520816A2 (en) | 2009-10-23 | 2019-08-07 | Millennium Pharmaceuticals, Inc. | Anti-gcc antibody molecules and related compositions and methods |
WO2011056497A1 (en) | 2009-10-26 | 2011-05-12 | Genentech, Inc. | Activin receptor type iib compositions and methods of use |
WO2011056502A1 (en) | 2009-10-26 | 2011-05-12 | Genentech, Inc. | Bone morphogenetic protein receptor type ii compositions and methods of use |
WO2011056494A1 (en) | 2009-10-26 | 2011-05-12 | Genentech, Inc. | Activin receptor-like kinase-1 antagonist and vegfr3 antagonist combinations |
EP3202898A1 (en) | 2009-11-02 | 2017-08-09 | University of Washington | Therapeutic nuclease compositions and methods |
US11306297B2 (en) | 2009-11-02 | 2022-04-19 | University Of Washington | Therapeutic nuclease compositions and methods |
US10000745B2 (en) | 2009-11-02 | 2018-06-19 | University Of Washington | Therapeutic nuclease compositions and methods |
WO2011053982A2 (en) | 2009-11-02 | 2011-05-05 | University Of Washington | Therapeutic nuclease compositions and methods |
US9790479B2 (en) | 2009-11-02 | 2017-10-17 | University Of Washington | Therapeutic nuclease compositions and methods |
EP3460056A1 (en) | 2009-11-02 | 2019-03-27 | University Of Washington | Therapeutic nuclease compositions and methods |
US8841416B2 (en) | 2009-11-02 | 2014-09-23 | University Of Washington | Therapeutic nuclease compositions and methods |
EP3594356A1 (en) | 2009-11-04 | 2020-01-15 | Merck Sharp & Dohme Corp. | Engineered anti-tslp antibody |
WO2011056772A1 (en) | 2009-11-04 | 2011-05-12 | Schering Corporation | Engineered anti-tslp antibody |
WO2011054030A1 (en) | 2009-11-05 | 2011-05-12 | Cephalon Australia Pty Ltd | Treatment of cancer involving mutated kras or braf genes |
US8932588B2 (en) | 2009-11-05 | 2015-01-13 | Teva Pharmaceuticals Australia Pty. Ltd. | Treatment of cancer involving mutated KRAS or BRAF genes |
WO2011057120A1 (en) | 2009-11-05 | 2011-05-12 | Genentech, Inc. | Methods and composition for secretion of heterologous polypeptides |
WO2011060015A1 (en) | 2009-11-11 | 2011-05-19 | Genentech, Inc. | Methods and compositions for detecting target proteins |
EP3279215A1 (en) | 2009-11-24 | 2018-02-07 | MedImmune Limited | Targeted binding agents against b7-h1 |
WO2011067711A2 (en) | 2009-12-01 | 2011-06-09 | Compugen Ltd | Novel heparanase splice variant |
WO2011068993A1 (en) | 2009-12-02 | 2011-06-09 | Acceleron Pharma Inc. | Compositions and methods for increasing serum half-life of fc fusion proteins. |
WO2011071577A1 (en) | 2009-12-11 | 2011-06-16 | Genentech, Inc. | Anti-vegf-c antibodies and methods using same |
WO2011076781A1 (en) | 2009-12-22 | 2011-06-30 | Novartis Ag | Tetravalent cd47-antibody constant region fusion protein for use in therapy |
WO2011079185A1 (en) | 2009-12-23 | 2011-06-30 | Genentech, Inc. | Anti-bv8 antibodies and uses thereof |
WO2011100403A1 (en) | 2010-02-10 | 2011-08-18 | Immunogen, Inc | Cd20 antibodies and uses thereof |
WO2011098449A1 (en) | 2010-02-10 | 2011-08-18 | Novartis Ag | Methods and compounds for muscle growth |
US8975376B2 (en) | 2010-02-23 | 2015-03-10 | Sanofi | Anti-alpha2 integrin antibodies and their uses |
EP3696194A1 (en) | 2010-02-23 | 2020-08-19 | F. Hoffmann-La Roche AG | Anti-angiogenesis therapy for the treatment of ovarian cancer |
EP3064509A2 (en) | 2010-02-23 | 2016-09-07 | F. Hoffmann-La Roche AG | Anti-angiogenesis therapy for the treatment of ovarian cancer |
WO2011106300A2 (en) | 2010-02-23 | 2011-09-01 | Genentech, Inc. | Anti-angiogenesis therapy for the treatment of ovarian cancer |
US11267891B2 (en) | 2010-02-23 | 2022-03-08 | Sanofi | Fc variant antibodies and their uses |
WO2011108502A1 (en) | 2010-03-02 | 2011-09-09 | 協和発酵キリン株式会社 | Modified antibody composition |
US10730945B2 (en) | 2010-03-04 | 2020-08-04 | Macrogenics, Inc. | Antibodies reactive with B7-H3 and users thereof |
US9896508B2 (en) | 2010-03-04 | 2018-02-20 | Macrogenics, Inc. | Antibodies reactive with B7-H3 and uses thereof |
US10683364B2 (en) | 2010-03-04 | 2020-06-16 | Macrogenics, Inc. | Antibodies reactive with B7-H3, immunologically active fragments thereof and uses thereof |
EP2982380A1 (en) | 2010-03-04 | 2016-02-10 | MacroGenics, Inc. | Antibodies reactive with b7-h3, immunologically active fragments thereof and uses thereof |
US9714295B2 (en) | 2010-03-04 | 2017-07-25 | Macrogenics, Inc. | Antibodies reactive with B7-H3, immunologically active fragments thereof and uses thereof |
US9714296B2 (en) | 2010-03-04 | 2017-07-25 | Macrogenics, Inc. | Antibodies reactive with B7-H3, immunologically active fragments thereof and uses thereof |
WO2011109400A2 (en) | 2010-03-04 | 2011-09-09 | Macrogenics,Inc. | Antibodies reactive with b7-h3, immunologically active fragments thereof and uses thereof |
US10745467B2 (en) | 2010-03-26 | 2020-08-18 | The Trustees Of Dartmouth College | VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders |
US10781254B2 (en) | 2010-03-26 | 2020-09-22 | The Trustees Of Dartmouth College | VISTA regulatory T cell mediator protein, VISTA binding agents and use thereof |
US9296815B2 (en) | 2010-03-29 | 2016-03-29 | Zymeworks Inc. | Antibodies with enhanced or suppressed effector function |
EP3208281A1 (en) | 2010-03-29 | 2017-08-23 | Zymeworks, Inc. | Antibodies with enhanced or suppressed effector function |
EP3181581A1 (en) | 2010-03-30 | 2017-06-21 | Chugai Seiyaku Kabushiki Kaisha | Antibodies with modified affinity to fcrn that promote antigen clearance |
WO2011122011A3 (en) * | 2010-03-30 | 2012-01-05 | Chugai Seiyaku Kabushiki Kaisha | Antibodies with modified affinity to fcrn that promote antigen clearance |
CN102918057A (en) * | 2010-03-30 | 2013-02-06 | 中外制药株式会社 | Antigen-binding molecules that promote antigen clearance |
EP3702368A1 (en) | 2010-03-30 | 2020-09-02 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecules that promote antigen clearance |
WO2011122011A2 (en) | 2010-03-30 | 2011-10-06 | Chugai Seiyaku Kabushiki Kaisha | Antibodies with modified affinity to fcrn that promote antigen clearance |
CN102918057B (en) * | 2010-03-30 | 2021-06-01 | 中外制药株式会社 | Antibodies with improved affinity for FcRn that promote antigen clearance |
EP4234698A2 (en) | 2010-05-06 | 2023-08-30 | Novartis AG | Compositions and methods of use for therapeutic low density lipoprotein-related protein 6 (lrp6) antibodies |
WO2011138392A1 (en) | 2010-05-06 | 2011-11-10 | Novartis Ag | Compositions and methods of use for therapeutic low density lipoprotein -related protein 6 (lrp6) antibodies |
WO2011138391A1 (en) | 2010-05-06 | 2011-11-10 | Novartis Ag | Compositions and methods of use for therapeutic low density lipoprotein - related protein 6 (lrp6) multivalent antibodies |
EP3345926A1 (en) | 2010-05-06 | 2018-07-11 | Novartis AG | Compositions and methods of use for therapeutic low density lipoprotein-related protein 6 (lrp6) antibodies |
WO2011146568A1 (en) | 2010-05-19 | 2011-11-24 | Genentech, Inc. | Predicting response to a her inhibitor |
US11959118B2 (en) | 2010-05-27 | 2024-04-16 | Merck Sharp & Dohme Llc | Fc-containing polypeptides having improved properties and comprising mutations at positions 243 and 264 of the Fc-region |
US10858686B2 (en) | 2010-05-27 | 2020-12-08 | Merck Sharp & Dohme Corp. | Method for preparing antibodies having improved properties |
WO2011153243A2 (en) | 2010-06-02 | 2011-12-08 | Genentech, Inc. | Anti-angiogenesis therapy for treating gastric cancer |
WO2011153224A2 (en) | 2010-06-02 | 2011-12-08 | Genentech, Inc. | Diagnostic methods and compositions for treatment of cancer |
WO2011153346A1 (en) | 2010-06-03 | 2011-12-08 | Genentech, Inc. | Immuno-pet imaging of antibodies and immunoconjugates and uses therefor |
EP3327035A1 (en) | 2010-06-22 | 2018-05-30 | Precision Biologics Inc. | Colon and pancreas cancer specific antigens and antibodies |
US10927362B2 (en) | 2010-07-09 | 2021-02-23 | Bioverativ Therapeutics Inc. | Processable single chain molecules and polypeptides made using same |
US10968442B2 (en) | 2010-07-09 | 2021-04-06 | Bioverativ Therapeutics Inc. | Chimeric clotting factors |
US9856468B2 (en) | 2010-07-09 | 2018-01-02 | Bioverativ Therapeutics Inc. | Processable single chain molecules and polypeptides made using same |
WO2012006633A1 (en) | 2010-07-09 | 2012-01-12 | Biogen Idec Hemophilia Inc. | Chimeric clotting factors |
WO2012006635A1 (en) | 2010-07-09 | 2012-01-12 | Biogen Idec Hemophilia Inc. | Processable single chain molecules and polypeptides made using same |
EP3560962A1 (en) | 2010-07-09 | 2019-10-30 | Bioverativ Therapeutics Inc. | Processable single chain molecules and polypeptides made using same |
EP2848939A1 (en) | 2010-07-19 | 2015-03-18 | F. Hoffmann-La Roche AG | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
WO2012010548A1 (en) | 2010-07-19 | 2012-01-26 | F. Hoffmann-La Roche Ag | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
EP2866032A1 (en) | 2010-07-19 | 2015-04-29 | F. Hoffmann-La Roche AG | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
EP2824457A1 (en) | 2010-07-19 | 2015-01-14 | F. Hoffmann-La Roche AG | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
WO2012010549A1 (en) | 2010-07-19 | 2012-01-26 | F. Hoffmann-La Roche Ag | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
WO2012010550A1 (en) | 2010-07-19 | 2012-01-26 | F. Hoffmann-La Roche Ag | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
EP2848940A1 (en) | 2010-07-19 | 2015-03-18 | F. Hoffmann-La Roche AG | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
WO2012010551A1 (en) | 2010-07-19 | 2012-01-26 | F. Hoffmann-La Roche Ag | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
WO2012010547A1 (en) | 2010-07-19 | 2012-01-26 | F. Hoffmann-La Roche Ag | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
EP2801826A1 (en) | 2010-07-19 | 2014-11-12 | F. Hoffmann-La Roche AG | Method to identify a patient with an increased likelihood of responding to an anti-cancer therapy |
EP3696195A1 (en) | 2010-07-23 | 2020-08-19 | Trustees of Boston University | Anti-despr inhibitors as therapeutics for inhibition of pathological angiogenesis and tumor cell invasiveness and for molecular imaging and targeted delivery |
WO2012012750A1 (en) | 2010-07-23 | 2012-01-26 | Trustees Of Boston University | ANTI-DEsupR INHIBITORS AS THERAPEUTICS FOR INHIBITION OF PATHOLOGICAL ANGIOGENESIS AND TUMOR CELL INVASIVENESS AND FOR MOLECULAR IMAGING AND TARGETED DELIVERY |
US9458216B2 (en) | 2010-07-29 | 2016-10-04 | Eleven Biotherapeutics, Inc. | Nucleic acid encoding chimeric IL-1 receptor type I antagonists |
EP4219538A2 (en) | 2010-07-29 | 2023-08-02 | Buzzard Pharmaceuticals AB | Receptor binding agents |
US8853150B2 (en) | 2010-07-29 | 2014-10-07 | Eleven Biotherapeutics, Inc. | Chimeric IL-1 receptor type I antagonists |
WO2012016203A1 (en) | 2010-07-29 | 2012-02-02 | Eleven Biotherapeutics, Inc. | Chimeric il-1 receptor type i agonists and antagonists |
WO2012016173A2 (en) | 2010-07-30 | 2012-02-02 | Ac Immune S.A. | Safe and functional humanized antibodies |
US9221900B2 (en) | 2010-07-30 | 2015-12-29 | Ac Immune S.A. | Methods for identifying safe and functional humanized antibodies |
WO2012018687A1 (en) | 2010-08-02 | 2012-02-09 | Macrogenics, Inc. | Covalent diabodies and uses thereof |
WO2012019061A2 (en) | 2010-08-05 | 2012-02-09 | Stem Centrx, Inc. | Novel effectors and methods of use |
WO2012022814A1 (en) | 2010-08-20 | 2012-02-23 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (her3) |
WO2012027723A1 (en) | 2010-08-27 | 2012-03-01 | Stem Centrx, Inc | Notum protein modulators and methods of use |
US9234039B2 (en) | 2010-08-31 | 2016-01-12 | Sanofi | Peptide or peptide complex binding to ALPHA2 integrin and methods and uses involving the same |
WO2012031273A2 (en) | 2010-09-03 | 2012-03-08 | Stem Centrx, Inc. | Novel modulators and methods of use |
WO2012032080A1 (en) | 2010-09-07 | 2012-03-15 | F-Star Biotechnologische Forschungs- Und Entwicklungsges.M.B.H | Stabilised human fc |
WO2012035518A1 (en) | 2010-09-17 | 2012-03-22 | Compugen Ltd. | Compositions and methods for treatment of drug resistant multiple myeloma |
WO2012040617A2 (en) | 2010-09-23 | 2012-03-29 | Neogenix Oncology, Inc. | Colon and pancreas cancer peptidomimetics |
WO2012041800A1 (en) | 2010-09-27 | 2012-04-05 | Morphosys Ag | Anti-cd38 antibody and lenalidomide or bortezomib for the treatment of multiple myeloma and nhl |
US10308722B2 (en) | 2010-09-27 | 2019-06-04 | Morphosys Ag | Method for the treament of multiple myeloma or non-hodgkins lymphoma with anti-CD38 antibody in combination with thalidomine, lenalidomids, or pomalidomide |
US9765152B2 (en) | 2010-09-27 | 2017-09-19 | Morphosys Ag | Method for the treatment of multiple myeloma or non-Hodgkins lymphoma with anti-CD38 antibody and bortezomib or carfilzomib |
WO2012047968A2 (en) | 2010-10-05 | 2012-04-12 | Genentech, Inc. | Mutant smoothened and methods of using the same |
WO2012045703A1 (en) | 2010-10-05 | 2012-04-12 | Novartis Ag | Anti-il12rbeta1 antibodies and their use in treating autoimmune and inflammatory disorders |
WO2012058768A1 (en) | 2010-11-05 | 2012-05-10 | Zymeworks Inc. | Stable heterodimeric antibody design with mutations in the fc domain |
US9562109B2 (en) | 2010-11-05 | 2017-02-07 | Zymeworks Inc. | Stable heterodimeric antibody design with mutations in the Fc domain |
US10875931B2 (en) | 2010-11-05 | 2020-12-29 | Zymeworks, Inc. | Stable heterodimeric antibody design with mutations in the Fc domain |
EP4029881A1 (en) | 2010-11-08 | 2022-07-20 | F. Hoffmann-La Roche AG | Subcutaneously administered anti-il-6 receptor antibody |
EP3351559A2 (en) | 2010-11-08 | 2018-07-25 | F. Hoffmann-La Roche AG | Subcutaneously administered anti-il-6 receptor antibody |
WO2012064627A2 (en) | 2010-11-08 | 2012-05-18 | Genentech, Inc. | Subcutaneously administered anti-il-6 receptor antibody |
EP2787007A2 (en) | 2010-11-08 | 2014-10-08 | F. Hoffmann-La Roche AG | Subcutaneously administered ANTI-IL-6 receptor antibody |
WO2012069433A2 (en) | 2010-11-23 | 2012-05-31 | Glaxo Group Limited | Antigen binding proteins |
WO2012071554A2 (en) | 2010-11-23 | 2012-05-31 | Alder Biopharmaceuticals, Inc. | Anti-il-6 antibodies for the treatment of oral mucositis |
EP2853542A1 (en) | 2010-11-24 | 2015-04-01 | Glaxo Group Limited | Multispecific antigen binding proteins targeting HGF |
WO2012069557A1 (en) | 2010-11-24 | 2012-05-31 | Glaxo Group Limited | Multispecific antigen binding proteins targeting hgf |
WO2012075037A1 (en) | 2010-11-30 | 2012-06-07 | Genentech, Inc. | Low affinity blood brain barrier receptor antibodies and uses therefor |
EP4231014A2 (en) | 2010-11-30 | 2023-08-23 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to plurality of antigen molecules repeatedly |
WO2012073992A1 (en) | 2010-11-30 | 2012-06-07 | 中外製薬株式会社 | Antigen-binding molecule capable of binding to plurality of antigen molecules repeatedly |
EP3208282A1 (en) | 2010-11-30 | 2017-08-23 | F. Hoffmann-La Roche AG | Low affinity anti transferrin receptor and their use to transfer therapeutic scfv across the blood brain barrier |
EP2647707B1 (en) | 2010-11-30 | 2018-09-12 | Chugai Seiyaku Kabushiki Kaisha | Cytotoxicity-inducing therapeutic agent |
US11891434B2 (en) | 2010-11-30 | 2024-02-06 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to plurality of antigen molecules repeatedly |
WO2012078813A2 (en) | 2010-12-08 | 2012-06-14 | Stem Centrx, Inc. | Novel modulators and methods of use |
WO2012118547A1 (en) | 2010-12-08 | 2012-09-07 | Stem Centrx, Inc. | Novel modulators and methods of use |
US9127060B2 (en) | 2010-12-15 | 2015-09-08 | Wyeth Llc | Anti-Notch1 antibodies |
EP2654780A4 (en) * | 2010-12-23 | 2015-03-18 | Janssen Biotech Inc | Active protease-resistant antibody fc mutants |
EP2654780A1 (en) * | 2010-12-23 | 2013-10-30 | Janssen Biotech, Inc. | Active protease-resistant antibody fc mutants |
AU2011349719B2 (en) * | 2010-12-23 | 2016-09-15 | Janssen Biotech, Inc. | Active protease-resistant antibody Fc mutants |
US9611328B2 (en) | 2010-12-23 | 2017-04-04 | Janssen Biotech, Inc. | Active protease-resistant antibody FC mutants |
WO2012092539A2 (en) | 2010-12-31 | 2012-07-05 | Takeda Pharmaceutical Company Limited | Antibodies to dll4 and uses thereof |
US10183998B2 (en) | 2011-01-14 | 2019-01-22 | Redwood Bioscience, Inc. | Aldehyde-tagged immunoglobulin polypeptides and methods of use thereof |
US10689447B2 (en) | 2011-02-04 | 2020-06-23 | Genentech, Inc. | Fc variants and methods for their production |
US11912773B2 (en) | 2011-02-04 | 2024-02-27 | Genentech, Inc. | Fc variants and methods for their production |
EP3763388A1 (en) | 2011-02-18 | 2021-01-13 | AbbVie Stemcentrx LLC | Novel modulators and methods of use |
WO2012112943A1 (en) | 2011-02-18 | 2012-08-23 | Stem Centrx, Inc. | Novel modulators and methods of use |
KR20140014167A (en) | 2011-02-25 | 2014-02-05 | 추가이 세이야쿠 가부시키가이샤 | Fcγriib-specific fc antibody |
KR20230005405A (en) | 2011-02-25 | 2023-01-09 | 추가이 세이야쿠 가부시키가이샤 | FcγRIIb-specific Fc antibody |
US10618965B2 (en) | 2011-02-25 | 2020-04-14 | Chugai Seiyaku Kabushiki Kaisha | Method for altering plasma retention and immunogenicity of antigen-binding molecule |
EP3604330A1 (en) | 2011-02-25 | 2020-02-05 | Chugai Seiyaku Kabushiki Kaisha | Fcgammariib-specific fc antibody |
US11718678B2 (en) | 2011-02-25 | 2023-08-08 | Chugai Seiyaku Kabushiki Kaisha | Method for altering plasma retention and immunogenicity of antigen-binding molecule |
WO2012115241A1 (en) | 2011-02-25 | 2012-08-30 | 中外製薬株式会社 | Fcγriib-specific fc antibody |
KR20200103845A (en) | 2011-02-25 | 2020-09-02 | 추가이 세이야쿠 가부시키가이샤 | FcγRIIb-specific Fc antibody |
WO2012118750A2 (en) | 2011-02-28 | 2012-09-07 | Genentech, Inc. | Biological markers and methods for predicting response to b-cell antagonists |
US8969526B2 (en) | 2011-03-29 | 2015-03-03 | Roche Glycart Ag | Antibody Fc variants |
KR20220075441A (en) | 2011-03-30 | 2022-06-08 | 추가이 세이야쿠 가부시키가이샤 | Method for altering plasma retention and immunogenicity of antigen-binding molecule |
KR20140015501A (en) | 2011-03-30 | 2014-02-06 | 추가이 세이야쿠 가부시키가이샤 | Retention of antigen-binding molecules in blood plasma and method for modifying immunogenicity |
KR20240027154A (en) | 2011-03-30 | 2024-02-29 | 추가이 세이야쿠 가부시키가이샤 | Method for altering plasma retention and immunogenicity of antigen-binding molecule |
WO2012133782A1 (en) | 2011-03-30 | 2012-10-04 | 中外製薬株式会社 | Retention of antigen-binding molecules in blood plasma and method for modifying immunogenicity |
EP3825325A2 (en) | 2011-03-30 | 2021-05-26 | Chugai Seiyaku Kabushiki Kaisha | Retention of antigen-binding molecules in blood plasma and method for modifying immunogenicity |
KR20200121900A (en) | 2011-03-30 | 2020-10-26 | 추가이 세이야쿠 가부시키가이샤 | Method for altering plasma retention and immunogenicity of antigen-binding molecule |
EP2698431B1 (en) | 2011-03-30 | 2020-09-09 | Chugai Seiyaku Kabushiki Kaisha | Retention of antigen-binding molecules in blood plasma and method for modifying immunogenicity |
EP3412309A1 (en) | 2011-03-31 | 2018-12-12 | F. Hoffmann-La Roche AG | Methods of administering beta7 integrin antagonists |
US10214579B2 (en) | 2011-04-13 | 2019-02-26 | Bristol-Myers Squibb Company | Fc fusion proteins comprising novel linkers or arrangements |
EP3415528A2 (en) | 2011-04-13 | 2018-12-19 | Bristol-Myers Squibb Company | Fc fusion proteins comprising novel linkers or arrangements |
WO2012142515A2 (en) | 2011-04-13 | 2012-10-18 | Bristol-Myers Squibb Company | Fc fusion proteins comprising novel linkers or arrangements |
EP3896083A1 (en) | 2011-04-13 | 2021-10-20 | Bristol-Myers Squibb Company | Fc fusion proteins comprising novel linkers or arrangements |
EP3144320A1 (en) | 2011-04-13 | 2017-03-22 | Bristol-Myers Squibb Company | Fc fusion proteins comprising novel linkers or arrangements |
US9469676B2 (en) | 2011-04-13 | 2016-10-18 | Bristol-Myers Squibb Company | Fc fusion proteins comprising novel linkers or arrangements |
WO2012140627A1 (en) | 2011-04-15 | 2012-10-18 | Compugen Ltd. | Polypeptides and polynucleotides, and uses thereof for treatment of immune related disorders and cancer |
WO2012145493A1 (en) | 2011-04-20 | 2012-10-26 | Amplimmune, Inc. | Antibodies and other molecules that bind b7-h1 and pd-1 |
EP3403672A1 (en) | 2011-04-20 | 2018-11-21 | Medlmmune, LLC | Antibodies and other molecules that bind b7-h1 and pd-1 |
WO2012146934A1 (en) | 2011-04-28 | 2012-11-01 | Michael Clark | Binding molecules with biased recognition |
EP3449933A1 (en) | 2011-04-29 | 2019-03-06 | University of Washington | Therapeutic nuclease compositions and methods |
US8937157B2 (en) | 2011-04-29 | 2015-01-20 | University Of Washington | Therapeutic nuclease compositions and methods |
WO2012149440A2 (en) | 2011-04-29 | 2012-11-01 | University Of Washington | Therapeutic nuclease compositions and methods |
US11034944B2 (en) | 2011-04-29 | 2021-06-15 | University Of Washington | Therapeutic nuclease compositions and methods |
US10202588B2 (en) | 2011-04-29 | 2019-02-12 | The University Of Washington | Therapeutic nuclease compositions and methods |
WO2012156309A1 (en) | 2011-05-13 | 2012-11-22 | Millegen | Antibodies against her3 |
WO2012162067A2 (en) | 2011-05-21 | 2012-11-29 | Macrogenics, Inc. | Cd3-binding molecules capable of binding to human and non-human cd3 |
WO2012162068A2 (en) | 2011-05-21 | 2012-11-29 | Macrogenics, Inc. | Deimmunized serum-binding domains and their use for extending serum half-life |
EP3492494A1 (en) | 2011-05-21 | 2019-06-05 | MacroGenics, Inc. | Cd3-binding molecules capable of binding to human and non-human cd3 |
WO2012162561A2 (en) | 2011-05-24 | 2012-11-29 | Zyngenia, Inc. | Multivalent and monovalent multispecific complexes and their uses |
US9328170B2 (en) | 2011-05-25 | 2016-05-03 | Merck Sharp & Dohme Corp. | Method for preparing Fc containing polypeptides having improved properties |
EP3527218A1 (en) | 2011-06-10 | 2019-08-21 | Bioverativ Therapeutics Inc. | Pro-coagulant compounds and methods of use thereof |
US9486507B2 (en) | 2011-06-10 | 2016-11-08 | Biogen Ma Inc. | Pro-coagulant compounds and methods of use thereof |
WO2012172495A1 (en) | 2011-06-14 | 2012-12-20 | Novartis Ag | Compositions and methods for antibodies targeting tem8 |
WO2012172521A1 (en) | 2011-06-16 | 2012-12-20 | Novartis Ag | Soluble proteins for use as therapeutics |
WO2012175692A1 (en) | 2011-06-22 | 2012-12-27 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-axl antibodies and uses thereof |
WO2012175691A1 (en) | 2011-06-22 | 2012-12-27 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-axl antibodies and uses thereof |
WO2013003625A2 (en) | 2011-06-28 | 2013-01-03 | Oxford Biotherapeutics Ltd. | Antibodies |
EP4011913A1 (en) | 2011-06-30 | 2022-06-15 | Chugai Seiyaku Kabushiki Kaisha | Heterodimerized polypeptide |
KR20140041787A (en) | 2011-06-30 | 2014-04-04 | 추가이 세이야쿠 가부시키가이샤 | Heterodimerized polypeptide |
WO2013002362A1 (en) | 2011-06-30 | 2013-01-03 | 中外製薬株式会社 | Heterodimerized polypeptide |
WO2013003680A1 (en) | 2011-06-30 | 2013-01-03 | Genentech, Inc. | Anti-c-met antibody formulations |
US9890218B2 (en) | 2011-06-30 | 2018-02-13 | Chugai Seiyaku Kabushiki Kaisha | Heterodimerized polypeptide |
WO2013006437A1 (en) | 2011-07-01 | 2013-01-10 | Novartis Ag | Method for treating metabolic disorders |
EP3970746A2 (en) | 2011-07-06 | 2022-03-23 | Genmab B.V. | Polypeptide variants and uses thereof |
WO2013004842A2 (en) | 2011-07-06 | 2013-01-10 | Genmab A/S | Antibody variants and uses thereof |
WO2013012733A1 (en) | 2011-07-15 | 2013-01-24 | Biogen Idec Ma Inc. | Heterodimeric fc regions, binding molecules comprising same, and methods relating thereto |
WO2013010955A1 (en) | 2011-07-15 | 2013-01-24 | Morphosys Ag | Antibodies that are cross-reactive for macrophage migration inhibitory factor (mif) and d-dopachrome tautomerase (d-dt) |
WO2013011076A2 (en) | 2011-07-19 | 2013-01-24 | Glaxo Group Limited | Antigen-binding proteins with increased fcrn binding |
EP3009450A1 (en) | 2011-07-19 | 2016-04-20 | Glaxo Group Limited | Liquid formulation comprising adalimumab and an acetate buffer |
WO2013014208A2 (en) | 2011-07-27 | 2013-01-31 | Glaxo Group Limited | Antigen binding constructs |
WO2013025779A1 (en) | 2011-08-15 | 2013-02-21 | Amplimmune, Inc. | Anti-b7-h4 antibodies and their uses |
WO2013025944A1 (en) | 2011-08-17 | 2013-02-21 | Genentech, Inc. | Inhibition of angiogenesis in refractory tumors |
US11186638B2 (en) | 2011-09-12 | 2021-11-30 | Genzyme Corporation | Anti-αβTCR antibody |
WO2013039954A1 (en) | 2011-09-14 | 2013-03-21 | Sanofi | Anti-gitr antibodies |
KR20220025928A (en) | 2011-09-30 | 2022-03-03 | 추가이 세이야쿠 가부시키가이샤 | Antigen-binding molecule inducing immune response to target antigen |
KR20200051048A (en) | 2011-09-30 | 2020-05-12 | 추가이 세이야쿠 가부시키가이샤 | Antigen-binding molecule for promoting elimination of antigens |
EP3939996A1 (en) | 2011-09-30 | 2022-01-19 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule promoting disappearance of antigens having plurality of biological activities |
WO2013047729A1 (en) | 2011-09-30 | 2013-04-04 | 中外製薬株式会社 | Antigen-binding molecule inducing immune response to target antigen |
CN110639014A (en) * | 2011-09-30 | 2020-01-03 | 中外制药株式会社 | Antigen binding molecules that promote antigen elimination |
WO2013046704A2 (en) | 2011-09-30 | 2013-04-04 | Chugai Seiyaku Kabushiki Kaisha | THERAPEUTIC ANTIGEN-BINDING MOLECULE WITH A FcRn-BINDING DOMAIN THAT PROMOTES ANTIGEN CLEARANCE |
WO2013047748A1 (en) | 2011-09-30 | 2013-04-04 | 中外製薬株式会社 | Antigen-binding molecule promoting disappearance of antigens having plurality of biological activities |
JPWO2013047729A1 (en) * | 2011-09-30 | 2015-03-26 | 中外製薬株式会社 | Antigen-binding molecules that induce immune responses to target antigens |
WO2013047752A1 (en) | 2011-09-30 | 2013-04-04 | 中外製薬株式会社 | Antigen-binding molecule for promoting loss of antigens |
KR20200096692A (en) | 2011-09-30 | 2020-08-12 | 추가이 세이야쿠 가부시키가이샤 | Antigen-binding molecule for promoting elimination of antigens |
EP3680251A1 (en) | 2011-09-30 | 2020-07-15 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecules for promoting elimination of antigens |
US10556949B2 (en) | 2011-09-30 | 2020-02-11 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule inducing immune response to target antigen |
KR20230066646A (en) | 2011-09-30 | 2023-05-16 | 추가이 세이야쿠 가부시키가이샤 | Antigen-binding molecule for promoting elimination of antigens |
US10253100B2 (en) | 2011-09-30 | 2019-04-09 | Chugai Seiyaku Kabushiki Kaisha | Therapeutic antigen-binding molecule with a FcRn-binding domain that promotes antigen clearance |
US10793633B2 (en) | 2011-09-30 | 2020-10-06 | Dana-Farber Cancer Institute, Inc. | Therapeutic peptides |
EP4324850A2 (en) | 2011-09-30 | 2024-02-21 | Chugai Seiyaku Kabushiki Kaisha | Therapeutic antigen-binding molecule with a fcrn-binding domain that promotes antigen clearance |
KR20210035312A (en) | 2011-09-30 | 2021-03-31 | 추가이 세이야쿠 가부시키가이샤 | Antigen-binding molecule inducing immune response to target antigen |
KR20140076594A (en) | 2011-09-30 | 2014-06-20 | 추가이 세이야쿠 가부시키가이샤 | Antigen-binding molecule inducing immune response to target antigen |
US11827699B2 (en) | 2011-09-30 | 2023-11-28 | Chugai Seiyaku Kabushiki Kaisha | Methods for producing antibodies promoting disappearance of antigens having plurality of biological activities |
EP3549956A2 (en) | 2011-09-30 | 2019-10-09 | Chugai Seiyaku Kabushiki Kaisha | Therapeutic antigen-binding molecule with a fcrn-binding domain that promotes antigen clearance |
EP3617313A1 (en) | 2011-10-05 | 2020-03-04 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule for promoting clearance from plasma of antigen comprising saccharide chain receptor-binding domain |
WO2013051294A1 (en) | 2011-10-05 | 2013-04-11 | 中外製薬株式会社 | Antigen-binding molecule for promoting clearance from plasma of antigen comprising saccharide chain receptor-binding domain |
EP3653222A1 (en) | 2011-10-14 | 2020-05-20 | Novartis AG | Antibodies and methods for wnt pathway-related diseases |
WO2013054307A2 (en) | 2011-10-14 | 2013-04-18 | Novartis Ag | Antibodies and methods for wnt pathway-related diseases |
US10981986B2 (en) | 2011-10-28 | 2021-04-20 | Teva Pharmaceuticals Australia Pty Ltd | Fusions of antibodies to CD38 and attenuated interferon alpha |
WO2013059885A2 (en) | 2011-10-28 | 2013-05-02 | Cephalon Australia Pty Ltd | Polypeptide constructs and uses thereof |
WO2013067060A1 (en) | 2011-11-01 | 2013-05-10 | Bionomics, Inc. | Anti-gpr49 antibodies |
US10598653B2 (en) | 2011-11-01 | 2020-03-24 | Bionomics Inc. | Methods of blocking cancer stem cell growth |
US10196442B2 (en) | 2011-11-01 | 2019-02-05 | Bionomics Inc. | Methods of inhibiting growth of a colon cancer tumor in a subject by administering monoclonal antibodies to G protein-coupled receptor 49 (GPR49) |
WO2013067054A1 (en) | 2011-11-01 | 2013-05-10 | Bionomics, Inc. | Antibodies and methods of treating cancer |
WO2013067057A1 (en) | 2011-11-01 | 2013-05-10 | Bionomics, Inc. | Anti-gpr49 antibodies |
WO2013067055A1 (en) | 2011-11-01 | 2013-05-10 | Bionomics, Inc. | Methods of blocking cancer stem cell growth |
WO2013063702A1 (en) | 2011-11-04 | 2013-05-10 | Zymeworks Inc. | Stable heterodimeric antibody design with mutations in the fc domain |
US10457742B2 (en) | 2011-11-04 | 2019-10-29 | Zymeworks Inc. | Stable heterodimeric antibody design with mutations in the Fc domain |
US9574010B2 (en) | 2011-11-04 | 2017-02-21 | Zymeworks Inc. | Stable heterodimeric antibody design with mutations in the Fc domain |
US9988460B2 (en) | 2011-11-04 | 2018-06-05 | Zymeworks Inc. | Crystal structures of heterodimeric Fc domains |
US9732155B2 (en) | 2011-11-04 | 2017-08-15 | Zymeworks Inc. | Crystal structures of heterodimeric Fc domains |
WO2013078170A1 (en) | 2011-11-21 | 2013-05-30 | Genentech, Inc. | Purification of anti-c-met antibodies |
WO2013078377A1 (en) | 2011-11-23 | 2013-05-30 | Igenica, Inc. | Anti-cd98 antibodies and methods of use thereof |
US11820793B2 (en) | 2011-11-30 | 2023-11-21 | Chugai Seiyaku Kabushiki Kaisha | Drug containing carrier into cell for forming immune complex |
WO2013081143A1 (en) | 2011-11-30 | 2013-06-06 | 中外製薬株式会社 | Drug containing carrier into cell for forming immune complex |
EP3517550A1 (en) | 2011-11-30 | 2019-07-31 | Chugai Seiyaku Kabushiki Kaisha | Drug containing carrier into cell for forming immune complex |
EP3590538A1 (en) | 2011-12-05 | 2020-01-08 | Novartis AG | Antibodies for epidermal growth factor receptor 3 (her3) |
WO2013084148A2 (en) | 2011-12-05 | 2013-06-13 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (her3) directed to domain ii of her3 |
WO2013085972A1 (en) | 2011-12-05 | 2013-06-13 | X-Body, Inc. | Pdgf receptor beta binding polypeptides |
WO2013084147A2 (en) | 2011-12-05 | 2013-06-13 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (her3) |
US11136398B2 (en) | 2011-12-05 | 2021-10-05 | X-Body, Inc. | PDGF receptor beta binding polypeptides |
US9217018B2 (en) | 2011-12-15 | 2015-12-22 | Sergei B Onikienko | HSP70 fusion protein conjugates and uses thereof |
EP3330288A1 (en) | 2011-12-21 | 2018-06-06 | Novartis AG | Compositions and methods for antibodies targeting factor p |
WO2013093762A1 (en) | 2011-12-21 | 2013-06-27 | Novartis Ag | Compositions and methods for antibodies targeting factor p |
WO2013093809A1 (en) | 2011-12-23 | 2013-06-27 | Pfizer Inc. | Engineered antibody constant regions for site-specific conjugation and methods and uses therefor |
WO2013100120A1 (en) | 2011-12-28 | 2013-07-04 | 中外製薬株式会社 | Humanized anti-epiregulin antibody, and cancer therapeutic agent comprising said antibody as active ingredient |
WO2013101771A2 (en) | 2011-12-30 | 2013-07-04 | Genentech, Inc. | Compositions and method for treating autoimmune diseases |
EP3663314A1 (en) | 2012-01-09 | 2020-06-10 | The Scripps Research Institute | Humanized antibodies with ultralong cdr3s |
WO2013106485A2 (en) | 2012-01-09 | 2013-07-18 | The Scripps Research Institute | Ultralong complementarity determining regions and uses thereof |
WO2013106489A1 (en) | 2012-01-09 | 2013-07-18 | The Scripps Research Institute | Humanized antibodies with ultralong cdr3s |
EP3505179A1 (en) | 2012-01-12 | 2019-07-03 | Bioverativ Therapeutics Inc. | Chimeric factor viii polypeptides and uses thereof |
US11370827B2 (en) | 2012-01-12 | 2022-06-28 | Bioverativ Therapeutics Inc. | Chimeric factor VIII polypeptides and uses thereof |
WO2013106765A1 (en) | 2012-01-13 | 2013-07-18 | Genentech, Inc. | Biological markers for identifying patients for treatment with vegf antagonists |
WO2013112467A1 (en) | 2012-01-23 | 2013-08-01 | Trustees Of Boston University | DEspR ANTAGONISTS AND AGONISTS AS THERAPEUTICS |
US9617336B2 (en) | 2012-02-01 | 2017-04-11 | Compugen Ltd | C10RF32 antibodies, and uses thereof for treatment of cancer |
WO2013119960A2 (en) | 2012-02-08 | 2013-08-15 | Stem Centrx, Inc. | Novel modulators and methods of use |
US10421798B2 (en) | 2012-02-15 | 2019-09-24 | Bioverativ Therapeutics Inc. | Factor VIII compositions and methods of making and using same |
US10370430B2 (en) | 2012-02-15 | 2019-08-06 | Bioverativ Therapeutics Inc. | Recombinant factor VIII proteins |
US11685771B2 (en) | 2012-02-15 | 2023-06-27 | Bioverativ Therapeutics Inc. | Recombinant factor VIII proteins |
WO2013125667A1 (en) | 2012-02-24 | 2013-08-29 | 中外製薬株式会社 | ANTIGEN-BINDING MOLECULE FOR PROMOTING DISAPPEARANCE OF ANTIGEN VIA FcγRIIB |
EP3738980A1 (en) | 2012-02-24 | 2020-11-18 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule for promoting disappearance of antigen via fc gamma riib |
EP3095797A1 (en) | 2012-02-24 | 2016-11-23 | Stemcentrx, Inc. | Anti dll3 antibodies and methods of use thereof |
EP3246339A1 (en) | 2012-03-28 | 2017-11-22 | Sanofi | Antibodies to bradykinin b1 receptor ligands |
WO2013148296A1 (en) | 2012-03-28 | 2013-10-03 | Sanofi | Antibodies to bradykinin b1 receptor ligands |
WO2013147153A1 (en) | 2012-03-29 | 2013-10-03 | 株式会社未来創薬研究所 | Anti-lamp5 antibody and utilization thereof |
WO2013148288A1 (en) | 2012-03-30 | 2013-10-03 | Genentech, Inc. | Diagnostic methods and compositions for treatment of cancer |
US9662405B2 (en) | 2012-04-26 | 2017-05-30 | Thomas Jefferson University | Method of treating cancer by administering chimeric antigen receptor comprising anti-GCC antibody |
US9156915B2 (en) | 2012-04-26 | 2015-10-13 | Thomas Jefferson University | Anti-GCC antibody molecules |
WO2013166290A1 (en) | 2012-05-04 | 2013-11-07 | Abbvie Biotherapeutics Inc. | P21 biomarker assay |
WO2013169657A1 (en) | 2012-05-07 | 2013-11-14 | Sanofi | Methods for preventing biofilm formation |
WO2013173687A1 (en) | 2012-05-18 | 2013-11-21 | Genentech, Inc. | High-concentration monoclonal antibody formulations |
EP3427721A1 (en) | 2012-05-18 | 2019-01-16 | Genentech, Inc. | High-concentration monoclonal antibody formulations |
WO2013177062A2 (en) | 2012-05-21 | 2013-11-28 | Genentech, Inc. | Methods for improving safety of blood-brain barrier transport |
EP2852618A2 (en) * | 2012-05-21 | 2015-04-01 | F. Hoffmann-La Roche AG | Methods for improving safety of blood-brain barrier transport |
US11167038B2 (en) | 2012-05-21 | 2021-11-09 | Genentech, Inc. | Methods for improving safety of blood-brain barrier transport |
EP3594239A1 (en) | 2012-05-21 | 2020-01-15 | F. Hoffmann-La Roche AG | Methods for improving safety of blood-brain barrier transport |
US10183995B2 (en) | 2012-05-23 | 2019-01-22 | Argen-X N.V. | IL-6 binding molecules |
WO2013174927A1 (en) | 2012-05-23 | 2013-11-28 | Novartis International Pharmaceutical Limited | Production of fucosylated glycoproteins |
WO2013175427A1 (en) | 2012-05-23 | 2013-11-28 | Argen-X B.V. | Il-6 binding molecules |
WO2013175276A1 (en) | 2012-05-23 | 2013-11-28 | Argen-X B.V | Il-6 binding molecules |
US11117959B2 (en) | 2012-05-23 | 2021-09-14 | Argenx Bvba | IL-6 binding molecules |
US11827701B2 (en) | 2012-05-23 | 2023-11-28 | argenx BV | IL-6 binding molecules |
WO2013177386A1 (en) | 2012-05-24 | 2013-11-28 | Abbvie Biotherapeutics Inc. | Biomarkers for predicting response to tweak receptor (tweakr) agonist therapy |
WO2013180201A1 (en) | 2012-05-30 | 2013-12-05 | 中外製薬株式会社 | Antigen-binding molecule for eliminating aggregated antigens |
WO2013180200A1 (en) | 2012-05-30 | 2013-12-05 | 中外製薬株式会社 | Target-tissue-specific antigen-binding molecule |
EP3795215A1 (en) | 2012-05-30 | 2021-03-24 | Chugai Seiyaku Kabushiki Kaisha | Target tissue-specific antigen-binding molecule |
EP3892638A1 (en) | 2012-05-30 | 2021-10-13 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule for eliminating aggregated antigens |
WO2013184514A1 (en) | 2012-06-04 | 2013-12-12 | Irm Llc | Site-specific labeling methods and molecules produced thereby |
WO2013185114A2 (en) | 2012-06-08 | 2013-12-12 | Biogen Idec Ma Inc. | Chimeric clotting factors |
US10287564B2 (en) | 2012-06-08 | 2019-05-14 | Bioverativ Therapeutics Inc. | Procoagulant compounds |
EP4079316A1 (en) | 2012-06-08 | 2022-10-26 | Bioverativ Therapeutics Inc. | Procoagulant compounds |
EP3693000A1 (en) | 2012-06-08 | 2020-08-12 | Bioverativ Therapeutics Inc. | Procoagulant compounds |
WO2013185113A1 (en) | 2012-06-08 | 2013-12-12 | Biogen Idec Ma Inc. | Procoagulant compounds |
US10202595B2 (en) | 2012-06-08 | 2019-02-12 | Bioverativ Therapeutics Inc. | Chimeric clotting factors |
WO2013183032A2 (en) | 2012-06-08 | 2013-12-12 | Glenmark Pharmaceuticals S.A. | Anti-trka antibodies with enhanced inhibitory properties and derivatives thereof |
US11261437B2 (en) | 2012-06-08 | 2022-03-01 | Bioverativ Therapeutics Inc. | Procoagulant compounds |
US11168316B2 (en) | 2012-06-08 | 2021-11-09 | Bioverativ Therapeutics, Inc. | Chimeric clotting factors |
JPWO2013187495A1 (en) * | 2012-06-14 | 2016-02-08 | 中外製薬株式会社 | Antigen binding molecules comprising modified Fc regions |
US11142563B2 (en) | 2012-06-14 | 2021-10-12 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule containing modified Fc region |
EP4310191A2 (en) | 2012-06-14 | 2024-01-24 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule containing modified fc region |
WO2013187495A1 (en) | 2012-06-14 | 2013-12-19 | 中外製薬株式会社 | ANTIGEN-BINDING MOLECULE CONTAINING MODIFIED Fc REGION |
WO2013192131A1 (en) * | 2012-06-21 | 2013-12-27 | Indiana University Research And Technology Corporation | Incretin receptor ligand polypeptide fc-region fusion polypeptides and conjugates with altered fc-effector function |
US11180557B2 (en) | 2012-06-22 | 2021-11-23 | King's College London | Vista modulators for diagnosis and treatment of cancer |
US11752189B2 (en) | 2012-06-22 | 2023-09-12 | The Trustees Of Dartmouth College | Vista antagonist and methods of use |
US10933115B2 (en) | 2012-06-22 | 2021-03-02 | The Trustees Of Dartmouth College | VISTA antagonist and methods of use |
US9499634B2 (en) | 2012-06-25 | 2016-11-22 | Zymeworks Inc. | Process and methods for efficient manufacturing of highly pure asymmetric antibodies in mammalian cells |
US10508154B2 (en) | 2012-06-25 | 2019-12-17 | Zymeworks Inc. | Process and methods for efficient manufacturing of highly pure asymmetric antibodies in mammalian cells |
EP3275899A1 (en) | 2012-07-02 | 2018-01-31 | Bristol-Myers Squibb Company | Optimization of antibodies that bind lymphocyte activation gene-3 (lag-3), and uses thereof |
WO2014008218A1 (en) | 2012-07-02 | 2014-01-09 | Bristol-Myers Squibb Company | Optimization of antibodies that bind lymphocyte activation gene-3 (lag-3), and uses thereof |
EP3795592A1 (en) | 2012-07-02 | 2021-03-24 | Bristol-Myers Squibb Company | Optimization of antibodies that bind lymphocyte activation gene-3 (lag-3), and uses thereof |
EP3404105A1 (en) | 2012-07-06 | 2018-11-21 | Bioverativ Therapeutics Inc. | Cell line expressing single chain factor viii polypeptides and uses thereof |
EP3632462A1 (en) | 2012-07-06 | 2020-04-08 | Genmab B.V. | Dimeric protein with triple mutations |
US11180572B2 (en) | 2012-07-06 | 2021-11-23 | Genmab B.V. | Dimeric protein with triple mutations |
US10023628B2 (en) | 2012-07-06 | 2018-07-17 | Bioverativ Therapeutics Inc. | Cell line expressing single chain factor VIII polypeptides and uses thereof |
WO2014006217A1 (en) | 2012-07-06 | 2014-01-09 | Genmab B.V. | Dimeric protein with triple mutations |
US10138291B2 (en) | 2012-07-11 | 2018-11-27 | Bioverativ Therapeutics Inc. | Factor VIII complex with XTEN and von Willebrand Factor protein, and uses thereof |
EP4269431A1 (en) | 2012-07-11 | 2023-11-01 | Bioverativ Therapeutics Inc. | Factor viii complex with xten and von willebrand factor protein, and uses thereof |
EP3674410A1 (en) | 2012-07-11 | 2020-07-01 | Bioverativ Therapeutics Inc. | Factor viii complex with xten and von willebrand factor protein, and uses thereof |
US11091534B2 (en) | 2012-07-11 | 2021-08-17 | Bioverativ Therapeutics Inc. | Factor VIII complex with XTEN and von Willebrand Factor protein, and uses thereof |
US9695233B2 (en) | 2012-07-13 | 2017-07-04 | Roche Glycart Ag | Bispecific anti-VEGF/anti-ANG-2 antibodies and their use in the treatment of ocular vascular diseases |
US10683345B2 (en) | 2012-07-13 | 2020-06-16 | Roche Glycart Ag | Bispecific anti-VEGF/anti-ANG-2 antibodies and their use in the treatment of ocular vascular diseases |
WO2014013019A1 (en) | 2012-07-18 | 2014-01-23 | Glycotope Gmbh | Novel therapeutic treatments with anti-her2 antibodies having a low fucosylation |
EP3381943A1 (en) | 2012-07-25 | 2018-10-03 | Celldex Therapeutics, Inc. | Anti-kit antibodies and uses thereof |
EP4063391A1 (en) | 2012-07-25 | 2022-09-28 | Celldex Therapeutics, Inc. | Anti-kit antibodies and uses thereof |
WO2014018625A1 (en) | 2012-07-25 | 2014-01-30 | Kolltan Pharmaceuticals, Inc. | Anti-kit antibodies and uses thereof |
WO2014029752A1 (en) | 2012-08-22 | 2014-02-27 | Glaxo Group Limited | Anti lrp6 antibodies |
KR20150045443A (en) | 2012-08-24 | 2015-04-28 | 추가이 세이야쿠 가부시키가이샤 | FcγRIIb-specific Fc region variant |
WO2014030728A1 (en) | 2012-08-24 | 2014-02-27 | 中外製薬株式会社 | Fcγriib-specific fc region variant |
KR20230110836A (en) | 2012-08-24 | 2023-07-25 | 추가이 세이야쿠 가부시키가이샤 | FcγRIIb-specific Fc region variant |
US10919953B2 (en) | 2012-08-24 | 2021-02-16 | Chugai Seiyaku Kabushiki Kaisha | FcgammaRIIB-specific Fc region variant |
US11236168B2 (en) | 2012-08-24 | 2022-02-01 | Chugai Seiyaku Kabushiki Kaisha | Mouse FcγammaRII-specific Fc antibody |
EP3721900A1 (en) | 2012-08-24 | 2020-10-14 | Chugai Seiyaku Kabushiki Kaisha | Fcgammariib-specific fc region variant |
WO2014030750A1 (en) | 2012-08-24 | 2014-02-27 | 中外製薬株式会社 | MOUSE FcγRII-SPECIFIC Fc ANTIBODY |
EP3597747A1 (en) | 2012-08-24 | 2020-01-22 | Chugai Seiyaku Kabushiki Kaisha | Mouse fcgammarii-specific fc antibody |
KR20210084688A (en) | 2012-08-24 | 2021-07-07 | 추가이 세이야쿠 가부시키가이샤 | FcγRIIb-specific Fc region variant |
WO2014033074A1 (en) | 2012-08-29 | 2014-03-06 | F. Hoffmann-La Roche Ag | Blood brain barrier shuttle |
US11529416B2 (en) | 2012-09-07 | 2022-12-20 | Kings College London | Vista modulators for diagnosis and treatment of cancer |
EP3725805A1 (en) | 2012-09-07 | 2020-10-21 | Novartis AG | Il-18 binding molecules |
WO2014037899A2 (en) | 2012-09-07 | 2014-03-13 | Novartis Ag | Il-18 binding molecules |
US10836813B2 (en) | 2012-09-12 | 2020-11-17 | Genzyme Corporation | Fc containing polypeptides with altered glycosylation and reduced effector function |
US9790268B2 (en) | 2012-09-12 | 2017-10-17 | Genzyme Corporation | Fc containing polypeptides with altered glycosylation and reduced effector function |
EP4223783A2 (en) | 2012-09-12 | 2023-08-09 | Genzyme Corporation | Fc containing polypeptides with altered glycosylation and reduced effector function |
WO2014059028A1 (en) | 2012-10-09 | 2014-04-17 | Igenica, Inc. | Anti-c16orf54 antibodies and methods of use thereof |
WO2014072876A1 (en) | 2012-11-09 | 2014-05-15 | Pfizer Inc. | Platelet-derived growth factor b specific antibodies and compositions and uses thereof |
EP2733153A1 (en) | 2012-11-15 | 2014-05-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the preparation of immunoconjugates and uses thereof |
US11078296B2 (en) | 2012-11-28 | 2021-08-03 | Zymeworks Inc. | Engineered immunoglobulin heavy chain-light chain pairs and uses thereof |
US9914785B2 (en) | 2012-11-28 | 2018-03-13 | Zymeworks Inc. | Engineered immunoglobulin heavy chain-light chain pairs and uses thereof |
WO2014084859A1 (en) | 2012-11-30 | 2014-06-05 | Novartis Ag | Molecules and methods for modulating tmem16a activities |
WO2014083379A1 (en) | 2012-11-30 | 2014-06-05 | Institut Pasteur | Use of anti-fcyri and/or anti-fcyriia antibodies for treating arthritis, inflammation, thrombocytopenia and allergic shock |
WO2014089111A1 (en) | 2012-12-05 | 2014-06-12 | Novartis Ag | Compositions and methods for antibodies targeting epo |
EP3851454A1 (en) | 2012-12-05 | 2021-07-21 | Novartis AG | Compositions and methods for antibodies targeting epo |
WO2014100483A1 (en) | 2012-12-19 | 2014-06-26 | Amplimmune, Inc. | Anti-human b7-h4 antibodies and their uses |
EP4119947A1 (en) | 2012-12-21 | 2023-01-18 | Chugai Seiyaku Kabushiki Kaisha | Gpc3-targeting drug which is administered to patient responsive to gpc3-targeting drug therapy |
WO2014097648A1 (en) | 2012-12-21 | 2014-06-26 | 中外製薬株式会社 | Gpc3-targeted therapeutic agent for administration to patients for whom gpc3-targeted therapeutic agent therapy is effective |
EP3557260A1 (en) | 2012-12-21 | 2019-10-23 | Chugai Seiyaku Kabushiki Kaisha | Gpc3-targeting drug which is administered to patient responsive to gpc3-targeting drug therapy |
WO2014100823A1 (en) | 2012-12-21 | 2014-06-26 | Amplimmune, Inc. | Anti-h7cr antibodies |
KR20150097786A (en) | 2012-12-27 | 2015-08-26 | 추가이 세이야쿠 가부시키가이샤 | Heterodimerized polypeptide |
WO2014104165A1 (en) | 2012-12-27 | 2014-07-03 | 中外製薬株式会社 | Heterodimerized polypeptide |
US10766960B2 (en) | 2012-12-27 | 2020-09-08 | Chugai Seiyaku Kabushiki Kaisha | Heterodimerized polypeptide |
EP3336104A1 (en) | 2012-12-28 | 2018-06-20 | Precision Biologics, Inc. | Humanized monoclonal antibodies and methods of use for the diagnosis and treatment of colon and pancreas cancer |
US9290576B2 (en) | 2013-01-02 | 2016-03-22 | Glenmark Pharmaceuticals S.A. | Antibodies that bind to TL1A and their uses |
WO2014108198A1 (en) | 2013-01-10 | 2014-07-17 | Genmab B.V. | Human igg1 fc region variants and uses thereof |
WO2014114651A1 (en) | 2013-01-24 | 2014-07-31 | Glaxosmithkline Intellectual Property Development Limited | Tnf-alpha antigen-binding proteins |
US10988537B2 (en) | 2013-02-01 | 2021-04-27 | Regeneren Pharmaceuticals, Inc. | Antibodies comprising chimeric constant domains |
US10106610B2 (en) | 2013-02-01 | 2018-10-23 | Regeneron Pharmaceuticals, Inc. | Antibodies comprising chimeric constant domains |
US9359437B2 (en) | 2013-02-01 | 2016-06-07 | Regeneron Pharmaceuticals, Inc. | Antibodies comprising chimeric constant domains |
US9963513B2 (en) | 2013-02-05 | 2018-05-08 | Engmab Sàrl | Method for the selection of antibodies against BCMA |
US10077315B2 (en) | 2013-02-05 | 2018-09-18 | Engmab Sàrl | Bispecific antibodies against CD3 and BCMA |
US10851171B2 (en) | 2013-02-05 | 2020-12-01 | Engmab Sarl | Method for the selection of antibodies against BCMA |
EP2762496A1 (en) | 2013-02-05 | 2014-08-06 | EngMab AG | Method for the selection of antibodies against BCMA |
EP3620468A1 (en) | 2013-02-05 | 2020-03-11 | EngMab Sàrl | Method for the selection of antibodies against bcma |
WO2014122143A1 (en) | 2013-02-05 | 2014-08-14 | Engmab Ag | Method for the selection of antibodies against bcma |
WO2014124258A2 (en) | 2013-02-08 | 2014-08-14 | Irm Llc | Specific sites for modifying antibodies to make immunoconjugates |
WO2015198217A2 (en) | 2013-02-08 | 2015-12-30 | Novartis Ag | Compositions and methods for long-acting antibodies targeting il-17 |
EP3929217A2 (en) | 2013-02-08 | 2021-12-29 | Novartis AG | Specific sites for modifying antibodies to make immunoconjugates |
WO2014122613A1 (en) | 2013-02-08 | 2014-08-14 | Novartis Ag | Anti-il-17a antibodies and their use in treating autoimmune and inflammatory disorders |
EP3656786A1 (en) | 2013-02-08 | 2020-05-27 | Novartis AG | Anti-il-17a antibodies and their use in treating autoimmune and inflammatory disorders |
WO2014124316A2 (en) | 2013-02-08 | 2014-08-14 | Irm Llc | Specific sites for modifying antibodies to make immunoconjugates |
WO2014126871A1 (en) | 2013-02-12 | 2014-08-21 | Bristol-Myers Squibb Company | Tangential flow filtration based protein refolding methods |
WO2014126884A1 (en) | 2013-02-12 | 2014-08-21 | Bristol-Myers Squibb Company | High ph protein refolding methods |
EP3617220A1 (en) | 2013-02-12 | 2020-03-04 | Bristol-Myers Squibb Company | High ph protein refolding methods |
EP3299378A1 (en) | 2013-02-12 | 2018-03-28 | Bristol-Myers Squibb Company | High ph protein refolding methods |
EP3744728A1 (en) | 2013-02-12 | 2020-12-02 | Bristol-Myers Squibb Company | Tangential flow filtration based protein refolding methods |
WO2014125041A1 (en) | 2013-02-14 | 2014-08-21 | Innate Pharma | Treatment of peripheral t cell lymphoma |
EP3255062A1 (en) | 2013-02-14 | 2017-12-13 | Innate Pharma | Treatment of peripheral t cell lymphoma |
EP3889173A1 (en) | 2013-02-15 | 2021-10-06 | Bioverativ Therapeutics Inc. | Optimized factor viii gene |
US11787851B2 (en) | 2013-02-15 | 2023-10-17 | Bioverativ Therapeutics Inc. | Optimized factor VIII gene |
WO2014127215A1 (en) | 2013-02-15 | 2014-08-21 | Biogen Idec Ma Inc. | Optimized factor viii gene |
US10370431B2 (en) | 2013-02-15 | 2019-08-06 | Bioverativ Therapeutics Inc. | Optimized factor VIII gene |
EP4223772A2 (en) | 2013-02-15 | 2023-08-09 | Bioverativ Therapeutics Inc. | Optimized factor viii gene |
EP3521312A1 (en) | 2013-02-20 | 2019-08-07 | Innate Pharma, S.A. | A compound that specifically binds to kir3dl2 for use in the treatment of peripheral t cell lymphoma |
EP3896088A1 (en) | 2013-02-20 | 2021-10-20 | Innate Pharma | Treatment of peripheral t cell lymphoma |
WO2014130879A2 (en) | 2013-02-22 | 2014-08-28 | Stem Centrx, Inc. | Novel antibody conjugates and uses thereof |
EP3556400A1 (en) | 2013-02-22 | 2019-10-23 | AbbVie Stemcentrx LLC | Method of making antidll3-antibody pbd conjugates |
WO2014130923A2 (en) | 2013-02-25 | 2014-08-28 | Genentech, Inc. | Methods and compositions for detecting and treating drug resistant akt mutant |
US10214589B2 (en) | 2013-03-11 | 2019-02-26 | Genzyme Corporation | Site-specific antibody-drug conjugation through glycoengineering |
US11130816B2 (en) | 2013-03-11 | 2021-09-28 | Genzyme Corporation | Site-specific antibody-drug conjugation through glycoengineering |
EP4063389A2 (en) | 2013-03-11 | 2022-09-28 | Genzyme Corporation | Site-specific antibody-drug conjugation through glycoengineering |
US9701753B2 (en) | 2013-03-11 | 2017-07-11 | Genzyme Corporation | Hyperglycosylated binding polypeptides |
WO2014164534A2 (en) | 2013-03-11 | 2014-10-09 | Genzyme Corporation | Site-specific antibody-drug conjugation through glycoengineering |
US11807690B2 (en) | 2013-03-11 | 2023-11-07 | Genzyme Corporation | Hyperglycosylated binding polypeptides |
US10494439B2 (en) | 2013-03-11 | 2019-12-03 | Genzyme Corporation | Hyperglycosylated binding polypeptides |
EP4098663A1 (en) | 2013-03-11 | 2022-12-07 | Genzyme Corporation | Hyperglycosylated binding polypeptides |
US9580511B2 (en) | 2013-03-11 | 2017-02-28 | Genzyme Corporation | Site-specific antibody-drug conjugation through glycoengineering |
WO2014164503A1 (en) | 2013-03-11 | 2014-10-09 | Genzyme Corporation | Hyperglycosylated binding polypeptides |
EP3424956A1 (en) | 2013-03-11 | 2019-01-09 | Genzyme Corporation | Hyperglycosylated binding polypeptides |
US10799589B2 (en) | 2013-03-13 | 2020-10-13 | Buzzard Pharmaceuticals AB | Chimeric cytokine formulations for ocular delivery |
WO2014160160A2 (en) | 2013-03-13 | 2014-10-02 | Novartis Ag | Antibody drug conjugates |
US10730947B2 (en) | 2013-03-14 | 2020-08-04 | Macrogenics, Inc. | Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor and an antigen expressed by a cell infected by a virus and uses thereof |
US11421031B2 (en) | 2013-03-14 | 2022-08-23 | Macrogenics, Inc. | Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor and an antigen expressed by a cell infected by a virus and uses thereof |
WO2014159239A2 (en) | 2013-03-14 | 2014-10-02 | Novartis Ag | Antibodies against notch 3 |
EP3611189A1 (en) | 2013-03-14 | 2020-02-19 | Novartis AG | Antibodies against notch 3 |
US9908938B2 (en) | 2013-03-14 | 2018-03-06 | Macrogenics, Inc. | Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor and an antigen expressed by a cell infected by a virus and uses thereof |
US10745483B2 (en) | 2013-03-15 | 2020-08-18 | Dana-Farber Cancer Institute, Inc. | Therapeutic peptides |
EP3611180A1 (en) | 2013-03-15 | 2020-02-19 | Daniel J. Capon | Hybrid immunoglobulin containing non-peptidyl linkage |
EP3712177A1 (en) | 2013-03-15 | 2020-09-23 | GlaxoSmithKline Intellectual Property Development Limited | Anti-lag-3 binding proteins |
WO2014145050A1 (en) | 2013-03-15 | 2014-09-18 | Atyr Pharma, Inc. | Histidyl-trna synthetase-fc conjugates |
WO2014144357A1 (en) | 2013-03-15 | 2014-09-18 | Merck Patent Gmbh | Tetravalent bispecific antibodies |
WO2014144911A2 (en) | 2013-03-15 | 2014-09-18 | Capon Daniel J | Hybrid immunoglobulin containing non-peptidyl linkage |
EP4039281A1 (en) | 2013-03-15 | 2022-08-10 | Biomolecular Holdings LLC | Hybrid immunoglobulin containing non-peptidyl linkage |
US10280221B2 (en) | 2013-03-15 | 2019-05-07 | Glaxosmithkline Intellectual Property Development Limited | Anti-LAG-3 binding proteins |
EP3514178A1 (en) | 2013-03-15 | 2019-07-24 | Novartis AG | Antibody drug conjugates |
EP3666886A1 (en) | 2013-03-15 | 2020-06-17 | Dana-Farber Cancer Institute, Inc. | Therapeutic peptides |
US10344088B2 (en) | 2013-03-15 | 2019-07-09 | Glaxosmithkline Intellectual Property Development Limited | Antigen binding proteins |
EP3424530A1 (en) | 2013-03-15 | 2019-01-09 | Zyngenia, Inc. | Multivalent and monovalent multispecific complexes and their uses |
EP3460054A1 (en) | 2013-03-15 | 2019-03-27 | Atyr Pharma, Inc. | Histidyl-trna synthetase-fc conjugates |
WO2014144791A2 (en) | 2013-03-15 | 2014-09-18 | Dana-Farber Cancer Institute, Inc. | Therapeutic peptides |
US11642398B2 (en) | 2013-03-15 | 2023-05-09 | Bioverativ Therapeutics Inc. | Factor IX polypeptide formulations |
WO2014140180A1 (en) | 2013-03-15 | 2014-09-18 | Glaxosmithkline Intellectual Property Development Limited | Anti-lag-3 binding proteins |
EP3933401A2 (en) | 2013-03-27 | 2022-01-05 | F. Hoffmann-La Roche AG | Use of biomarkers for assessing treatment of gastrointestinal inflammatory disorders with beta7 integrin antagonists |
EP3495814A2 (en) | 2013-03-27 | 2019-06-12 | F. Hoffmann-La Roche AG | Use of biomarkers for assessing treatment of gastrointestinal inflammatory disorders with beta7 integrin antagonists |
US11267868B2 (en) | 2013-04-02 | 2022-03-08 | Chugai Seiyaku Kabushiki Kaisha | Fc region variant |
WO2014173886A1 (en) | 2013-04-22 | 2014-10-30 | Glycotope Gmbh | Anti-cancer treatments with anti-egfr antibodies having a low fucosylation |
WO2014178820A1 (en) | 2013-04-29 | 2014-11-06 | Teva Pharmaceuticals Australia Pty Ltd. | Anti-cd38 antibodies and fusions to attenuated interferon alpha-2b |
EP3677591A1 (en) | 2013-04-29 | 2020-07-08 | Teva Pharmaceuticals Australia Pty Ltd | Anti-cd38 antibodies and fusions to attenuated interferon alpha-2b |
US11117975B2 (en) | 2013-04-29 | 2021-09-14 | Teva Pharmaceuticals Australia Pty Ltd | Anti-CD38 antibodies and fusions to attenuated interferon alpha-2B |
US9963515B2 (en) | 2013-04-29 | 2018-05-08 | Teva Pharmaceuticals Australia Pty Ltd. | Anti-CD38 antibodies and fusions to attenuated interferon alpha-2B |
EP4324480A2 (en) | 2013-05-20 | 2024-02-21 | F. Hoffmann-La Roche AG | Anti-transferrin receptor antibodies and methods of use |
EP3594240A1 (en) | 2013-05-20 | 2020-01-15 | F. Hoffmann-La Roche AG | Anti-transferrin receptor antibodies and methods of use |
US10053510B2 (en) | 2013-05-24 | 2018-08-21 | Promis Neurosciences Inc. | FasR antibodies and methods of use |
WO2014190356A2 (en) | 2013-05-24 | 2014-11-27 | Amplimmune, Inc. | Anti-b7-h5 antibodies and their uses |
US11098105B2 (en) | 2013-05-31 | 2021-08-24 | Zymeworks Inc. | Heteromultimers with reduced or silenced effector function |
WO2014205300A2 (en) | 2013-06-21 | 2014-12-24 | Novartis Ag | Lectin-like oxidized ldl receptor1 antibodies and methods of use |
WO2014205302A2 (en) | 2013-06-21 | 2014-12-24 | Novartis Ag | Lectin-like oxidized ldl receptor1 antibodies and methods of use |
WO2014208482A1 (en) | 2013-06-24 | 2014-12-31 | 中外製薬株式会社 | Therapeutic agent comprising humanized anti-epiregulin antibody as active ingredient for non-small-cell lung carcinoma excluding adenocarcinoma |
WO2015017146A2 (en) | 2013-07-18 | 2015-02-05 | Fabrus, Inc. | Antibodies with ultralong complementarity determining regions |
WO2015010100A2 (en) | 2013-07-18 | 2015-01-22 | Fabrus, Inc. | Humanized antibodies with ultralong complementarity determining regions |
EP3875106A1 (en) | 2013-08-08 | 2021-09-08 | Bioverativ Therapeutics Inc. | Purification of chimeric fviii molecules |
US10947269B2 (en) | 2013-08-08 | 2021-03-16 | Bioverativ Therapeutics Inc. | Purification of chimeric FVIII molecules |
US10344092B2 (en) | 2013-08-09 | 2019-07-09 | Macrogenics, Inc. | Bi-specific monovalent Fc diabodies that are capable of binding CD32B and CD79b and uses thereof |
US11384149B2 (en) | 2013-08-09 | 2022-07-12 | Macrogenics, Inc. | Bi-specific monovalent Fc diabodies that are capable of binding CD32B and CD79b and uses thereof |
US10947591B2 (en) | 2013-08-12 | 2021-03-16 | Genentech, Inc. | Compositions and method for treating complement-associated conditions |
US10093978B2 (en) | 2013-08-12 | 2018-10-09 | Genentech, Inc. | Compositions for detecting complement factor H (CFH) and complement factor I (CFI) polymorphisms |
WO2015023596A1 (en) | 2013-08-12 | 2015-02-19 | Genentech, Inc. | Compositions and method for treating complement-associated conditions |
US9845363B2 (en) | 2013-08-13 | 2017-12-19 | Sanofi | Antibodies to plasminogen activator inhibitor-1 (PAI-1) and uses thereof |
EP3620472A1 (en) | 2013-08-13 | 2020-03-11 | Sanofi | Antibodies to plasminogen activator inhibitor-1 (pai-1) and uses thereof |
WO2015023891A2 (en) | 2013-08-14 | 2015-02-19 | Biogen Idec Ma Inc. | Factor viii-xten fusions and uses thereof |
WO2015022658A2 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Methods of treating sporadic inclusion body myositis |
US10548953B2 (en) | 2013-08-14 | 2020-02-04 | Bioverativ Therapeutics Inc. | Factor VIII-XTEN fusions and uses thereof |
US9822181B2 (en) | 2013-08-23 | 2017-11-21 | Macrogenics, Inc. | Bi-specific monovalent diabodies that are capable of binding CD123 and CD3, and uses thereof |
US10858430B2 (en) | 2013-08-23 | 2020-12-08 | Macrogenics, Inc. | Bi-specific monovalent diabodies that are capable of binding to gpA33 and CD3, and uses thereof |
US9932400B2 (en) | 2013-08-23 | 2018-04-03 | Macrogenics, Inc. | Bi-specific monovalent diabodies that are capable of binding to gpA33 and CD3, and uses thereof |
US10787521B2 (en) | 2013-08-23 | 2020-09-29 | Macrogenics, Inc. | Bi-specific monovalent diabodies that are capable of binding CD123 and CD3, and uses thereof |
EP3338793A1 (en) | 2013-08-28 | 2018-06-27 | AbbVie Stemcentrx LLC | Novel sez6 modulators and methods of use |
EP3892294A1 (en) | 2013-08-28 | 2021-10-13 | AbbVie Stemcentrx LLC | Site-specific antibody conjugation methods and compositions |
WO2015031673A2 (en) | 2013-08-28 | 2015-03-05 | Bioasis Technologies Inc. | Cns-targeted conjugates having modified fc regions and methods of use thereof |
US11578098B2 (en) | 2013-09-25 | 2023-02-14 | Bioverativ Therapeutics Inc. | On-column viral inactivation methods |
US10611794B2 (en) | 2013-09-25 | 2020-04-07 | Bioverativ Therapeutics Inc. | On-column viral inactivation methods |
EP3903599A1 (en) | 2013-09-25 | 2021-11-03 | Bioverativ Therapeutics Inc. | On-column viral inactivation methods |
WO2015046467A1 (en) | 2013-09-27 | 2015-04-02 | 中外製薬株式会社 | Method for producing polypeptide heteromultimer |
WO2015066557A1 (en) | 2013-10-31 | 2015-05-07 | Resolve Therapeutics, Llc | Therapeutic nuclease molecules with altered glycosylation and methods |
US10988745B2 (en) | 2013-10-31 | 2021-04-27 | Resolve Therapeutics, Llc | Therapeutic nuclease-albumin fusions and methods |
US10053511B2 (en) | 2013-11-06 | 2018-08-21 | Abbvie Stemcentrx Llc | Anti-claudin antibodies and methods of use |
WO2015067986A1 (en) | 2013-11-07 | 2015-05-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Neuregulin allosteric anti-her3 antibody |
US10584147B2 (en) | 2013-11-08 | 2020-03-10 | Biovertiv Therapeutics Inc. | Procoagulant fusion compound |
US11739149B2 (en) | 2013-11-11 | 2023-08-29 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule containing modified antibody variable region |
KR20160083094A (en) | 2013-11-11 | 2016-07-11 | 추가이 세이야쿠 가부시키가이샤 | Antigen-binding molecule containing modified antibody variable region |
KR20230104764A (en) | 2013-11-11 | 2023-07-10 | 추가이 세이야쿠 가부시키가이샤 | Antigen-binding molecule containing modified antibody variable region |
WO2015068847A1 (en) | 2013-11-11 | 2015-05-14 | 中外製薬株式会社 | Antigen-binding molecule containing modified antibody variable region |
WO2015073580A1 (en) | 2013-11-13 | 2015-05-21 | Pfizer Inc. | Tumor necrosis factor-like ligand 1a specific antibodies and compositions and uses thereof |
EP3763813A1 (en) | 2013-12-04 | 2021-01-13 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecules, the antigen-binding activity of which varies according to the concentration of compounds, and libraries of said molecules |
WO2015083764A1 (en) | 2013-12-04 | 2015-06-11 | 中外製薬株式会社 | Antigen-binding molecules, the antigen-binding activity of which varies according to the concentration of compounds, and libraries of said molecules |
WO2015085210A1 (en) | 2013-12-06 | 2015-06-11 | Dana-Farber Cancer Institute, Inc. | Therapeutic peptides |
US10106611B2 (en) | 2013-12-06 | 2018-10-23 | Dana-Farber Cancer Institute, Inc. | Antibodies that bind to MHC class I polypeptide-related sequence A |
EP3611191A1 (en) | 2013-12-09 | 2020-02-19 | Allakos Inc. | Anti-siglec-8 antibodies and methods of use thereof |
US9546215B2 (en) | 2013-12-09 | 2017-01-17 | Allakos Inc. | Anti-Siglec-8 antibodies and methods of use thereof |
WO2015089117A1 (en) | 2013-12-09 | 2015-06-18 | Allakos Inc. | Anti-siglec-8 antibodies and methods of use thereof |
WO2015089375A1 (en) | 2013-12-13 | 2015-06-18 | The General Hospital Corporation | Soluble high molecular weight (hmw) tau species and applications thereof |
EP3527587A1 (en) | 2013-12-17 | 2019-08-21 | F. Hoffmann-La Roche AG | Combination therapy comprising ox40 binding agonists and pd-l1 binding antagonists |
WO2015095423A2 (en) | 2013-12-17 | 2015-06-25 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
US10465000B2 (en) | 2013-12-20 | 2019-11-05 | Hoffmann-La Roche Inc. | Humanized anti-Tau(pS422) antibodies and methods of use |
EP3626738A1 (en) | 2013-12-24 | 2020-03-25 | Argenx BVBA | Fcrn antagonists and methods of use |
US11505585B2 (en) | 2013-12-24 | 2022-11-22 | argenx BV | FcRn antagonists and methods of use |
WO2015100299A1 (en) | 2013-12-24 | 2015-07-02 | Argen-X N.V. | Fcrn antagonists and methods of use |
US11242392B2 (en) | 2013-12-24 | 2022-02-08 | Janssen Pharmaceutica Nv | Anti-vista antibodies and fragments |
US11014987B2 (en) | 2013-12-24 | 2021-05-25 | Janssen Pharmaceutics Nv | Anti-vista antibodies and fragments, uses thereof, and methods of identifying same |
EP4176894A1 (en) | 2014-01-10 | 2023-05-10 | Bioverativ Therapeutics Inc. | Factor viii chimeric proteins and uses thereof |
US11192936B2 (en) | 2014-01-10 | 2021-12-07 | Bioverativ Therapeutics Inc. | Factor VIII chimeric proteins and uses thereof |
WO2015106052A1 (en) | 2014-01-10 | 2015-07-16 | Biogen Ma Inc. | Factor viii chimeric proteins and uses thereof |
EP4389139A2 (en) | 2014-01-10 | 2024-06-26 | Bioverativ Therapeutics Inc. | Factor viii chimeric proteins and uses thereof |
WO2015109212A1 (en) | 2014-01-17 | 2015-07-23 | Pfizer Inc. | Anti-il-2 antibodies and compositions and uses thereof |
EP3738981A1 (en) | 2014-01-24 | 2020-11-18 | NGM Biopharmaceuticals, Inc. | Antibodies binding beta klotho domain 2 and methods of use thereof |
WO2015120075A2 (en) | 2014-02-04 | 2015-08-13 | Genentech, Inc. | Mutant smoothened and methods of using the same |
US10100115B2 (en) | 2014-02-14 | 2018-10-16 | Macrogenics, Inc. | Methods for the treatment of vascularizing cancers |
US10183996B2 (en) | 2014-02-28 | 2019-01-22 | Allakos Inc. | Methods and compositions for treating Siglec-8 associated diseases |
WO2015131155A1 (en) | 2014-02-28 | 2015-09-03 | Allakos Inc. | Methods and compositions for treating siglec-8 associated diseases |
EP4014995A1 (en) | 2014-02-28 | 2022-06-22 | Allakos Inc. | Methods and compositions for treating siglec-8 associated diseases |
WO2015138615A2 (en) | 2014-03-12 | 2015-09-17 | Irm Llc | Specific sites for modifying antibodies to make immunoconjugates |
EP3960767A2 (en) | 2014-03-12 | 2022-03-02 | Novartis AG | Specific sites for modifying antibodies to make immunoconjugates |
WO2015139046A1 (en) | 2014-03-14 | 2015-09-17 | Genentech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
US10279021B2 (en) | 2014-03-14 | 2019-05-07 | Dana-Faber Cancer Institute, Inc. | Vaccine compositions and methods for restoring NKG2D pathway function against cancers |
EP4169944A1 (en) | 2014-03-14 | 2023-04-26 | Biomolecular Holdings LLC | Process for preparing hybrid immunoglobulin containing non-peptidyl linkage |
EP3572431A1 (en) | 2014-03-14 | 2019-11-27 | Innate Pharma | Humanized antibodies with stability |
EP3701971A1 (en) | 2014-03-14 | 2020-09-02 | Daniel J. Capon | Compounds useful in preparing hybrid immunoglobulin containing non-peptidyl linkage |
US11434300B2 (en) | 2014-03-19 | 2022-09-06 | Regeneron Pharmaceuticals, Inc. | Methods and antibody compositions for tumor treatment |
EP4015535A1 (en) | 2014-03-19 | 2022-06-22 | Genzyme Corporation | Site-specific glycoengineering of targeting moieties |
US10995148B2 (en) | 2014-03-19 | 2021-05-04 | Genzyme Corporation | Site-specific glycoengineering of targeting moieties |
US11697690B2 (en) | 2014-03-19 | 2023-07-11 | Genzyme Corporation | Site-specific glycoengineering of targeting moieties |
US10550193B2 (en) | 2014-03-19 | 2020-02-04 | Regeneron Pharmaceuticals, Inc. | Methods and antibody compositions for tumor treatment |
WO2015143271A1 (en) | 2014-03-21 | 2015-09-24 | X-Body, Inc. | Bi-specific antigen-binding polypeptides |
EP3712176A1 (en) | 2014-03-21 | 2020-09-23 | X-Body, Inc. | Bi-specific antigen-binding polypeptides |
WO2015148809A1 (en) | 2014-03-27 | 2015-10-01 | Genentech, Inc. | Methods for diagnosing and treating inflammatory bowel disease |
EP3632934A1 (en) | 2014-03-31 | 2020-04-08 | F. Hoffmann-La Roche AG | Anti-ox40 antibodies and methods of use |
WO2015153514A1 (en) | 2014-03-31 | 2015-10-08 | Genentech, Inc. | Combination therapy comprising anti-angiogenesis agents and ox40 binding agonists |
WO2015153513A1 (en) | 2014-03-31 | 2015-10-08 | Genentech, Inc. | Anti-ox40 antibodies and methods of use |
US10730951B2 (en) | 2014-03-31 | 2020-08-04 | Genentech, Inc. | Anti-OX40 antibodies and methods of use |
US9975957B2 (en) | 2014-03-31 | 2018-05-22 | Genentech, Inc. | Anti-OX40 antibodies and methods of use |
US10358500B2 (en) | 2014-04-04 | 2019-07-23 | Bionomics Inc. | Humanized antibodies that bind LGR5 |
US11485790B2 (en) | 2014-04-07 | 2022-11-01 | Chugai Seiyaku Kabushiki Kaisha | Immunoactivating antigen-binding molecule |
WO2015157592A1 (en) | 2014-04-11 | 2015-10-15 | Medimmune, Llc | Bispecific her2 antibodies |
WO2015164330A1 (en) | 2014-04-21 | 2015-10-29 | Millennium Pharmaceuticals, Inc. | Anti-psyk antibody molecules and use of same for syk-targeted therapy |
EP3461495A1 (en) | 2014-04-24 | 2019-04-03 | Novartis AG | Methods of improving or accelerating physical recovery after surgery for hip fracture |
WO2015162590A1 (en) | 2014-04-24 | 2015-10-29 | Novartis Ag | Methods of improving or accelerating physical recovery after surgery for hip fracture |
US11253591B2 (en) | 2014-05-01 | 2022-02-22 | Teva Pharmaceuticals Australia Pty Ltd. | Combination of lenalidomide and polypeptide construct, and uses thereof |
US10232041B2 (en) | 2014-05-01 | 2019-03-19 | Teva Pharmaceuticals Pty Ltd | Combination of lenalidomide and polypeptide construct, and uses thereof |
US9636334B2 (en) | 2014-05-01 | 2017-05-02 | Teva Pharmaceuticals Australia Pty Ltd | Combination of lenalidomide and polypeptide construct, and uses thereof |
US10179821B2 (en) | 2014-05-01 | 2019-01-15 | Genentech, Inc. | Anti-factor D antibodies |
US11760807B2 (en) | 2014-05-08 | 2023-09-19 | Chugai Seiyaku Kabushiki Kaisha | GPC3-targeting drug which is administered to patient responsive to GPC3-targeting drug therapy |
US11505605B2 (en) | 2014-05-13 | 2022-11-22 | Chugai Seiyaku Kabushiki Kaisha | T cell-redirected antigen-binding molecule for cells having immunosuppression function |
US11708404B2 (en) | 2014-05-16 | 2023-07-25 | Ablynx N.V. | Immunoglobulin variable domains |
US11897962B2 (en) | 2014-05-28 | 2024-02-13 | Agenus Inc. | Anti-GITR antibodies and methods of use thereof |
US10800849B2 (en) | 2014-05-28 | 2020-10-13 | Agenus Inc. | Anti-GITR antibodies and methods of use thereof |
US10829559B2 (en) | 2014-05-28 | 2020-11-10 | Agenus Inc. | Anti-GITR antibodies and methods of use thereof |
EP3498295A1 (en) | 2014-05-28 | 2019-06-19 | Agenus Inc. | Anti-gitr antibodies and methods of use thereof |
US10155818B2 (en) | 2014-05-28 | 2018-12-18 | Agenus Inc. | Anti-GITR antibodies and methods of use thereof |
US10280226B2 (en) | 2014-05-28 | 2019-05-07 | Agenus Inc. | Anti-GITR antibodies and methods of use thereof |
US11401335B2 (en) | 2014-05-28 | 2022-08-02 | Agenus Inc. | Anti-GITR antibodies and methods of use thereof |
WO2015184099A1 (en) | 2014-05-28 | 2015-12-03 | 4-Antibody Ag | Anti-gitr antibodies and methods of use thereof |
US10577426B2 (en) | 2014-05-28 | 2020-03-03 | Agenus Inc. | Anti-GITR antibodies and methods of use thereof |
EP3954703A2 (en) | 2014-05-29 | 2022-02-16 | MacroGenics, Inc. | Tri-specific binding molecules and methods of use thereof |
WO2015184203A1 (en) | 2014-05-29 | 2015-12-03 | Macrogenics, Inc. | Tri-specific binding molecules and methods of use thereof |
US11820818B2 (en) | 2014-05-29 | 2023-11-21 | Macrogenics, Inc. | Multi-chain polypeptide-containing tri-specific binding molecules |
US10647768B2 (en) | 2014-05-29 | 2020-05-12 | Macrogenics, Inc. | Multi-chain polypeptide-containing tri-specific binding molecules |
WO2015184207A1 (en) | 2014-05-29 | 2015-12-03 | Macrogenics, Inc. | Tri-specific binding molecules that specifically bind to multiple cancer antigens and methods of use thereof |
US10633440B2 (en) | 2014-05-29 | 2020-04-28 | Macrogenics, Inc. | Multi-chain polypeptide-containing tri-specific binding molecules that specifically bind to multiple cancer antigens |
US11697684B2 (en) | 2014-05-29 | 2023-07-11 | Macrogenics, Inc. | Tri-specific binding molecules that specifically bind to multiple cancer antigens |
US10584171B2 (en) | 2014-05-30 | 2020-03-10 | Henlix Biotech Co., Ltd. | Anti-epidermal growth factor receptor (EGFR) antibodies |
US11261255B2 (en) | 2014-05-30 | 2022-03-01 | Shanghai Henlius Biotech, Inc. | Anti-epidermal growth factor receptor (EGFR) antibodies |
EP3613433A1 (en) | 2014-05-30 | 2020-02-26 | Henlix Biotech Co., Ltd. | Anti-epidermal growth factor receptor (egfr) antibodies |
EP3998079A1 (en) | 2014-06-06 | 2022-05-18 | Bristol-Myers Squibb Company | Antibodies against glucocorticoid-induced tumor necrosis factor receptor (gitr) and uses thereof |
EP3610924A1 (en) | 2014-06-06 | 2020-02-19 | Bristol-Myers Squibb Company | Antibodies against glucocorticoid-induced tumor necrosis factor receptor (gitr) and uses thereof |
WO2015187835A2 (en) | 2014-06-06 | 2015-12-10 | Bristol-Myers Squibb Company | Antibodies against glucocorticoid-induced tumor necrosis factor receptor (gitr) and uses thereof |
US11123426B2 (en) | 2014-06-11 | 2021-09-21 | The Trustees Of Dartmouth College | Use of vista agonists and antagonists to suppress or enhance humoral immunity |
US10251952B2 (en) | 2014-06-26 | 2019-04-09 | Hoffmann-La Roche Inc. | Humanized anti-tau(pS422) antibody brain shuttles and use thereof |
US10519234B2 (en) | 2014-06-27 | 2019-12-31 | Innate Pharma | NKp46 binding proteins |
US11208480B2 (en) | 2014-06-27 | 2021-12-28 | Innate Pharma | Multispecific antigen binding proteins |
US11008561B2 (en) | 2014-06-30 | 2021-05-18 | Bioverativ Therapeutics Inc. | Optimized factor IX gene |
WO2016020791A1 (en) | 2014-08-05 | 2016-02-11 | Novartis Ag | Ckit antibody drug conjugates |
WO2016020880A2 (en) | 2014-08-07 | 2016-02-11 | Novartis Ag | Angiopoietin-like 4 antibodies and methods of use |
EP4122957A1 (en) | 2014-08-07 | 2023-01-25 | Novartis AG | Angiopoietin-like 4 antibodies and methods of use |
WO2016020882A2 (en) | 2014-08-07 | 2016-02-11 | Novartis Ag | Angiopoetin-like 4 (angptl4) antibodies and methods of use |
WO2016024195A1 (en) | 2014-08-12 | 2016-02-18 | Novartis Ag | Anti-cdh6 antibody drug conjugates |
US10238748B2 (en) | 2014-08-12 | 2019-03-26 | Novartis Ag | Anti-CDH6 antibody drug conjugates |
US9982045B2 (en) | 2014-08-12 | 2018-05-29 | Novartis Ag | Anti-CDH6 antibody drug conjugates |
WO2016028672A1 (en) | 2014-08-19 | 2016-02-25 | Merck Sharp & Dohme Corp. | Anti-lag3 antibodies and antigen-binding fragments |
EP3834842A1 (en) | 2014-08-19 | 2021-06-16 | Merck Sharp & Dohme Corp. | Anti-lag3 antibodies and antigen-binding fragments |
WO2016028656A1 (en) | 2014-08-19 | 2016-02-25 | Merck Sharp & Dohme Corp. | Anti-tigit antibodies |
WO2016030488A1 (en) | 2014-08-27 | 2016-03-03 | Innate Pharma | Treatment of celiac disease |
US10363496B2 (en) | 2014-09-05 | 2019-07-30 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Method for purification of monoclonal antibodies |
US10428156B2 (en) | 2014-09-05 | 2019-10-01 | Abbvie Stemcentrx Llc | Anti-MFI2 antibodies and methods of use |
US11001643B2 (en) | 2014-09-26 | 2021-05-11 | Chugai Seiyaku Kabushiki Kaisha | Cytotoxicity-inducing therapeutic agent |
WO2016046301A1 (en) | 2014-09-26 | 2016-03-31 | Bayer Pharma Aktiengesellschaft | Stabilized adrenomedullin derivatives and use thereof |
US10717778B2 (en) | 2014-09-29 | 2020-07-21 | Duke University | Bispecific molecules comprising an HIV-1 envelope targeting arm |
WO2016057841A1 (en) | 2014-10-08 | 2016-04-14 | Novartis Ag | Compositions and methods of use for augmented immune response and cancer therapy |
WO2016057846A1 (en) | 2014-10-08 | 2016-04-14 | Novartis Ag | Compositions and methods of use for augmented immune response and cancer therapy |
US11160874B2 (en) | 2014-10-09 | 2021-11-02 | Genzyme Corporation | Glycoengineered antibody drug conjugates |
EP3799887A1 (en) | 2014-10-09 | 2021-04-07 | Genzyme Corporation | Glycoengineered antibody drug conjugates |
US10064952B2 (en) | 2014-10-09 | 2018-09-04 | Genzyme Corporation | Glycoengineered antibody drug conjugates |
US11584923B2 (en) | 2014-10-14 | 2023-02-21 | Halozyme, Inc. | Compositions of adenosine deaminase-2 (ADA2), variants thereof and methods of using same |
WO2016061286A2 (en) | 2014-10-14 | 2016-04-21 | Halozyme, Inc. | Compositions of adenosine deaminase-2 (ada2), variants thereof and methods of using same |
US9969998B2 (en) | 2014-10-14 | 2018-05-15 | Halozyme, Inc. | Compositions of adenosine deaminase-2 (ADA2), variants thereof and methods of using same |
US10640564B2 (en) | 2014-10-17 | 2020-05-05 | Ichnos Sciences SA | Antibodies that bind to CCR6 and their uses |
EP3659625A1 (en) | 2014-10-23 | 2020-06-03 | Innate Pharma | Treatment of cancers using anti-nkg2a agents |
WO2016062851A1 (en) | 2014-10-23 | 2016-04-28 | Innate Pharma | Treatment of cancers using anti-nkg2a agents |
US11319356B2 (en) | 2014-10-29 | 2022-05-03 | Teva Pharmaceuticals Australia Pty Ltd | Interferon alpha 2B variants |
US10544199B2 (en) | 2014-10-29 | 2020-01-28 | Teva Pharmaceuticals Australia Pty Ltd | Interferon alpha 2B variants |
US10767232B2 (en) | 2014-11-03 | 2020-09-08 | Genentech, Inc. | Methods and biomarkers for predicting efficacy and evaluation of an OX40 agonist treatment |
US10845364B2 (en) | 2014-11-03 | 2020-11-24 | Genentech, Inc. | Assays for detecting T cell immune subsets and methods of use thereof |
WO2016073378A1 (en) | 2014-11-03 | 2016-05-12 | Genentech, Inc. | Assays for detecting t cell immune subsets and methods of use thereof |
US10208120B2 (en) | 2014-11-05 | 2019-02-19 | Genentech, Inc. | Anti-FGFR2/3 antibodies and methods using same |
US11154615B2 (en) | 2014-11-11 | 2021-10-26 | Chugai Seiyaku Kabushiki Kaisha | Library of antigen-binding molecules including modified antibody variable region |
EP3789403A1 (en) | 2014-11-11 | 2021-03-10 | MedImmune Limited | Therapeutic combinations comprising anti-cd73 antibodies and a2a receptor inhibitor and uses thereof |
WO2016075670A1 (en) | 2014-11-14 | 2016-05-19 | Novartis Ag | Antibody drug conjugates |
WO2016081384A1 (en) | 2014-11-17 | 2016-05-26 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
US10662244B2 (en) | 2014-11-17 | 2020-05-26 | Regeneron Pharmaceuticals, Inc. | Methods for tumor treatment using CD3XCD20 bispecific antibody |
WO2016079597A1 (en) | 2014-11-19 | 2016-05-26 | Axon Neuroscience Se | Humanized tau antibodies in alzheimer's disease |
WO2016081640A1 (en) | 2014-11-19 | 2016-05-26 | Genentech, Inc. | Anti-transferrin receptor / anti-bace1 multispecific antibodies and methods of use |
WO2016081643A1 (en) | 2014-11-19 | 2016-05-26 | Genentech, Inc. | Anti-transferrin receptor antibodies and methods of use |
EP3786182A1 (en) | 2014-11-19 | 2021-03-03 | Axon Neuroscience SE | Humanized tau antibodies in alzheimer's disease |
US10653791B2 (en) | 2014-11-21 | 2020-05-19 | Bristol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
US11352440B2 (en) | 2014-11-21 | 2022-06-07 | Bristol-Myers Squibb Company | Antibodies against CD73 and uses thereof |
US10100129B2 (en) | 2014-11-21 | 2018-10-16 | Bristol-Myers Squibb Company | Antibodies against CD73 and uses thereof |
EP3725808A1 (en) | 2014-11-21 | 2020-10-21 | Bristol-Myers Squibb Company | Antibodies against cd73 and uses thereof |
WO2016081748A2 (en) | 2014-11-21 | 2016-05-26 | Bristol-Myers Squibb Company | Antibodies against cd73 and uses thereof |
EP3789399A1 (en) | 2014-11-21 | 2021-03-10 | Bristol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
US9605080B2 (en) | 2014-11-21 | 2017-03-28 | Bristol-Myers Squibb Company | Antibodies against CD73 |
US10167343B2 (en) | 2014-11-21 | 2019-01-01 | Bristol-Myers Squibb Company | Antibodies against CD73 |
US10370455B2 (en) | 2014-12-05 | 2019-08-06 | Immunext, Inc. | Identification of VSIG8 as the putative VISTA receptor (V-R) and use thereof to produce VISTA/VSIG8 agonists and antagonists |
WO2016091891A1 (en) | 2014-12-09 | 2016-06-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Human monoclonal antibodies against axl |
WO2016094566A2 (en) | 2014-12-10 | 2016-06-16 | Genentech, Inc. | Blood brain barrier receptor antibodies and methods of use |
EP3633371A1 (en) | 2014-12-18 | 2020-04-08 | F. Hoffmann-La Roche AG | Assay and method for determining cdc eliciting antibodies |
WO2016097865A1 (en) | 2014-12-19 | 2016-06-23 | Regenesance B.V. | Antibodies that bind human c6 and uses thereof |
WO2016098079A2 (en) | 2014-12-19 | 2016-06-23 | Novartis Ag | Compositions and methods for antibodies targeting bmp6 |
US10738111B2 (en) | 2014-12-19 | 2020-08-11 | Chugai Seiyaku Kabushiki Kaisha | Anti-myostatin antibodies, polypeptides containing variant Fc regions, and methods of use |
KR20240042169A (en) | 2014-12-19 | 2024-04-01 | 추가이 세이야쿠 가부시키가이샤 | Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use |
EP3945096A1 (en) | 2014-12-19 | 2022-02-02 | Regenesance B.V. | Antibodies that bind human c6 and uses thereof |
US10000560B2 (en) | 2014-12-19 | 2018-06-19 | Chugai Seiyaku Kabushiki Kaisha | Anti-myostatin antibodies, polypeptides containing variant Fc regions, and methods of use |
KR20220034918A (en) | 2014-12-19 | 2022-03-18 | 추가이 세이야쿠 가부시키가이샤 | Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use |
US11454633B2 (en) | 2014-12-19 | 2022-09-27 | Chugai Seiyaku Kabushiki Kaisha | Anti-myostatin antibodies, polypeptides containing variant Fc regions, and methods of use |
EP4249066A2 (en) | 2014-12-23 | 2023-09-27 | Bristol-Myers Squibb Company | Antibodies to tigit |
WO2016115345A1 (en) | 2015-01-14 | 2016-07-21 | The Brigham And Women's Hospital, | Treatment of cancer with anti-lap monoclonal antibodies |
US10501552B2 (en) | 2015-01-26 | 2019-12-10 | Macrogenics, Inc. | Multivalent molecules comprising DR5-binding domains |
US11236391B2 (en) | 2015-01-28 | 2022-02-01 | Genentech, Inc. | Gene expression markers and treatment of multiple sclerosis |
WO2016123329A2 (en) | 2015-01-28 | 2016-08-04 | Genentech, Inc. | Gene expression markers and treatment of multiple sclerosis |
WO2016126972A1 (en) | 2015-02-04 | 2016-08-11 | Genentech, Inc. | Mutant smoothened and methods of using the same |
US10519229B2 (en) | 2015-02-05 | 2019-12-31 | Chugai Seiyaku Kabushiki Kaisha | Nucleic acids encoding IL-8 antibodies |
WO2016125495A1 (en) | 2015-02-05 | 2016-08-11 | Chugai Seiyaku Kabushiki Kaisha | Antibodies comprising an ion concentration dependent antigen-binding domain, fc region variants, il-8-binding antibodies, and uses therof |
KR20210009435A (en) | 2015-02-05 | 2021-01-26 | 추가이 세이야쿠 가부시키가이샤 | Antibodies comprising an ion concentration dependent antigen-binding domain, fc region variants, il-8-binding antibodies, and uses therof |
US11180548B2 (en) | 2015-02-05 | 2021-11-23 | Chugai Seiyaku Kabushiki Kaisha | Methods of neutralizing IL-8 biological activity |
EP3816179A2 (en) | 2015-02-05 | 2021-05-05 | Chugai Seiyaku Kabushiki Kaisha | Fc region variant comprising a modified fcrn-binding domain |
US9969800B2 (en) | 2015-02-05 | 2018-05-15 | Chugai Seiyaku Kabushiki Kaisha | IL-8 antibodies |
WO2016134333A1 (en) | 2015-02-19 | 2016-08-25 | Compugen Ltd. | Anti-pvrig antibodies and methods of use |
EP3295951A1 (en) | 2015-02-19 | 2018-03-21 | Compugen Ltd. | Anti-pvrig antibodies and methods of use |
EP3978929A1 (en) | 2015-02-19 | 2022-04-06 | Compugen Ltd. | Pvrig polypeptides and methods of treatment |
WO2016134335A2 (en) | 2015-02-19 | 2016-08-25 | Compugen Ltd. | Pvrig polypeptides and methods of treatment |
EP3653221A1 (en) | 2015-02-19 | 2020-05-20 | Compugen Ltd. | Anti-pvrig antibodies and methods of use |
EP4129320A1 (en) | 2015-02-19 | 2023-02-08 | Compugen Ltd. | Anti-pvrig antibodies and methods of use |
EP3978530A1 (en) | 2015-02-26 | 2022-04-06 | F. Hoffmann-La Roche AG | Integrin beta7 antagonists and methods of treating crohn's disease |
WO2016135066A1 (en) | 2015-02-26 | 2016-09-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Fusion proteins and antibodies comprising thereof for promoting apoptosis |
WO2016138207A1 (en) | 2015-02-26 | 2016-09-01 | Genentech, Inc. | Integrin beta7 antagonists and methods of treating crohn's disease |
EP4006051A1 (en) | 2015-03-09 | 2022-06-01 | Argenx BVBA | Methods of reducing serum levels of fc-containing agents using fcrn antagonists |
WO2016142782A1 (en) | 2015-03-09 | 2016-09-15 | Argen-X N.V. | Methods of reducing serum levels of fc-containing agents using fcrn antagonsits |
US10556952B2 (en) | 2015-03-30 | 2020-02-11 | Regeneron Pharmaceuticals, Inc. | Heavy chain constant regions with reduced binding to Fc gamma receptors |
US11518807B2 (en) | 2015-03-30 | 2022-12-06 | Regeneron Pharmaceuticals, Inc. | Heavy chain constant regions with reduced binding to Fc gamma receptors |
US10239946B2 (en) | 2015-03-31 | 2019-03-26 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Cell line overexpressing human CD303 antigen |
US10611843B2 (en) | 2015-03-31 | 2020-04-07 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Anti-CD303 monoclonal antibodies |
US10011658B2 (en) | 2015-04-03 | 2018-07-03 | Eureka Therapeutics, Inc. | Constructs targeting AFP peptide/MHC complexes and uses thereof |
US10865248B2 (en) | 2015-04-07 | 2020-12-15 | Genentech, Inc. | Antigen binding complex having agonistic activity and methods of use |
US11319359B2 (en) | 2015-04-17 | 2022-05-03 | Alpine Immune Sciences, Inc. | Immunomodulatory proteins with tunable affinities |
WO2016168771A2 (en) | 2015-04-17 | 2016-10-20 | Alpine Immune Sciences, Inc. | Immunomodulatory proteins with tunable affinities |
EP3875477A1 (en) | 2015-04-17 | 2021-09-08 | Alpine Immune Sciences, Inc. | Immunomodulatory proteins with tunable affinities |
WO2016179517A1 (en) | 2015-05-07 | 2016-11-10 | Agenus Inc. | Anti-ox40 antibodies and methods of use thereof |
WO2016188911A1 (en) | 2015-05-22 | 2016-12-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Human monoclonal antibodies fragments inhibiting both the cath-d catalytic activity and its binding to the lrp1 receptor |
US11384144B2 (en) | 2015-05-22 | 2022-07-12 | Memorial Sloan-Kettering Cancer Center | T cell receptor-like antibodies specific for a PRAME peptide |
EP3763827A1 (en) | 2015-05-29 | 2021-01-13 | F. Hoffmann-La Roche AG | Pd-l1 promoter methylation in cancer |
WO2016196381A1 (en) | 2015-05-29 | 2016-12-08 | Genentech, Inc. | Pd-l1 promoter methylation in cancer |
WO2016196228A1 (en) | 2015-05-29 | 2016-12-08 | Bristol-Myers Squibb Company | Antibodies against ox40 and uses thereof |
US11254987B2 (en) | 2015-05-29 | 2022-02-22 | Genentech, Inc. | PD-L1 promoter methylation in cancer |
EP3636660A1 (en) | 2015-05-30 | 2020-04-15 | Molecular Templates, Inc. | De-immunized, shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same |
EP3660035A1 (en) | 2015-05-30 | 2020-06-03 | Molecular Templates, Inc. | De-immunized, shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same |
WO2016196344A1 (en) | 2015-05-30 | 2016-12-08 | Molecular Templates, Inc. | De-immunized, shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same |
WO2016193872A2 (en) | 2015-06-05 | 2016-12-08 | Novartis Ag | Antibodies targeting bone morphogenetic protein 9 (bmp9) and methods therefor |
US11072653B2 (en) | 2015-06-08 | 2021-07-27 | Macrogenics, Inc. | LAG-3-binding molecules and methods of use thereof |
US11858991B2 (en) | 2015-06-08 | 2024-01-02 | Macrogenics, Inc. | LAG-3-binding molecules and methods of use thereof |
EP4303235A2 (en) | 2015-06-08 | 2024-01-10 | MacroGenics, Inc. | Lag-3-binding moleculkes and methods of use thereof |
WO2016200836A1 (en) | 2015-06-08 | 2016-12-15 | Genentech, Inc. | Methods of treating cancer using anti-ox40 antibodies |
WO2016200835A1 (en) | 2015-06-08 | 2016-12-15 | Genentech, Inc. | Methods of treating cancer using anti-ox40 antibodies and pd-1 axis binding antagonists |
WO2016203432A1 (en) | 2015-06-17 | 2016-12-22 | Novartis Ag | Antibody drug conjugates |
US10774145B2 (en) | 2015-06-17 | 2020-09-15 | Allakos Inc. | Methods and compositions for treating fibrotic diseases |
US11267897B2 (en) | 2015-06-23 | 2022-03-08 | Innate Pharma | Multispecific NK engager protein |
WO2016207278A1 (en) | 2015-06-23 | 2016-12-29 | Innate Pharma | Multispecific nk engager proteins |
WO2016207273A2 (en) | 2015-06-23 | 2016-12-29 | Innate Pharma | Multispecific antigen binding proteins |
US11584793B2 (en) | 2015-06-24 | 2023-02-21 | Hoffmann-La Roche Inc. | Anti-transferrin receptor antibodies with tailored affinity |
US10822402B2 (en) | 2015-06-24 | 2020-11-03 | Hoffmann-La Roche Inc. | Humanized anti-tau(pS422) antibodies and methods of use |
US11009509B2 (en) | 2015-06-24 | 2021-05-18 | Janssen Pharmaceutica Nv | Anti-VISTA antibodies and fragments |
US10465011B2 (en) | 2015-06-26 | 2019-11-05 | Novartis Ag | Factor XI antibodies and methods of use |
WO2016207858A1 (en) | 2015-06-26 | 2016-12-29 | Novartis Ag | Factor xi antibodies and methods of use |
EP3971211A1 (en) | 2015-07-13 | 2022-03-23 | Compugen Ltd. | Hide1 compositions and methods |
WO2017009712A1 (en) | 2015-07-13 | 2017-01-19 | Compugen Ltd. | Hide1 compositions and methods |
US11230605B2 (en) * | 2015-07-22 | 2022-01-25 | Inatherys | Anti-TfR antibodies and their use in treating proliferative and inflammatory disorders |
WO2017015619A1 (en) | 2015-07-23 | 2017-01-26 | The Regents Of The University Of California | Antibodies to coagulation factor xia and uses thereof |
US11466093B2 (en) | 2015-07-27 | 2022-10-11 | The General Hospital Corporation | Antibody derivatives with conditionally enabled effector function |
EP3981792A1 (en) | 2015-07-30 | 2022-04-13 | MacroGenics, Inc. | Pd-1-binding molecules and methods of use thereof |
EP3456346A1 (en) | 2015-07-30 | 2019-03-20 | MacroGenics, Inc. | Pd-1 and lag-3 binding molecules and methods of use thereof |
US11623959B2 (en) | 2015-07-30 | 2023-04-11 | Macrogenics, Inc. | PD-1-binding molecules and methods of use thereof |
WO2017019846A1 (en) | 2015-07-30 | 2017-02-02 | Macrogenics, Inc. | Pd-1-binding molecules and methods use thereof |
US10577422B2 (en) | 2015-07-30 | 2020-03-03 | Macrogenics, Inc. | PD-1-binding molecules and methods of use thereof |
US12018077B2 (en) | 2015-07-31 | 2024-06-25 | Memorial Sloan-Kettering Cancer Center | Methods of treatments using antigen-binding proteins targeting CD56 |
WO2017023859A1 (en) | 2015-07-31 | 2017-02-09 | Memorial Sloan-Kettering Cancer Center | Antigen-binding proteins targeting cd56 and uses thereof |
US10730941B2 (en) | 2015-07-31 | 2020-08-04 | Memorial Sloan-Kettering Cancer Center | Antigen-binding proteins targeting CD56 and uses thereof |
WO2017021893A1 (en) | 2015-08-03 | 2017-02-09 | Novartis Ag | Methods of treating fgf21-associated disorders |
EP3670535A1 (en) | 2015-08-03 | 2020-06-24 | EngMab Sàrl | Monoclonal antibodies against bcma |
US10745680B2 (en) | 2015-08-03 | 2020-08-18 | Bioverativ Therapeutics Inc. | Factor IX fusion proteins and methods of making and using same |
WO2017040790A1 (en) | 2015-09-01 | 2017-03-09 | Agenus Inc. | Anti-pd-1 antibodies and methods of use thereof |
US11680104B2 (en) | 2015-09-02 | 2023-06-20 | Immutep S.A.S. | Anti-LAG-3 antibodies |
EP3842457A1 (en) | 2015-09-09 | 2021-06-30 | Novartis AG | Thymic stromal lymphopoietin (tslp)-binding molecules and methods of using the molecules |
WO2017042701A1 (en) | 2015-09-09 | 2017-03-16 | Novartis Ag | Thymic stromal lymphopoietin (tslp)-binding antibodies and methods of using the antibodies |
WO2017046746A1 (en) | 2015-09-15 | 2017-03-23 | Acerta Pharma B.V. | Therapeutic combinations of a btk inhibitor and a gitr binding molecule, a 4-1bb agonist, or an ox40 agonist |
WO2017046676A1 (en) | 2015-09-16 | 2017-03-23 | Novartis Ag | Polyomavirus neutralizing antibodies |
KR20180125036A (en) | 2015-09-18 | 2018-11-21 | 추가이 세이야쿠 가부시키가이샤 | Il-8-binding antibodies and uses thereof |
WO2017046994A1 (en) | 2015-09-18 | 2017-03-23 | Chugai Seiyaku Kabushiki Kaisha | Il-8-binding antibodies and uses thereof |
KR20230079500A (en) | 2015-09-18 | 2023-06-07 | 추가이 세이야쿠 가부시키가이샤 | Il-8-binding antibodies and uses thereof |
WO2017049024A1 (en) | 2015-09-18 | 2017-03-23 | Cephalon, Inc. | Antibodies that specifically bind to tl1a |
EP3693393A1 (en) | 2015-09-18 | 2020-08-12 | Cephalon, Inc. | Antibodies that specifically bind to tl1a |
US11352426B2 (en) | 2015-09-21 | 2022-06-07 | Aptevo Research And Development Llc | CD3 binding polypeptides |
US10428145B2 (en) | 2015-09-29 | 2019-10-01 | Celgene Corporation | PD-1 binding proteins and methods of use thereof |
US10941205B2 (en) | 2015-10-02 | 2021-03-09 | Hoffmann-La Roche Inc. | Bispecific anti-human A-beta/human transferrin receptor antibodies and methods of use |
US11603411B2 (en) | 2015-10-02 | 2023-03-14 | Hoffmann-La Roche Inc. | Bispecific anti-human CD20/human transferrin receptor antibodies and methods of use |
US12030952B2 (en) | 2015-10-02 | 2024-07-09 | Hoffmann-La Roche Inc. | Bispecific anti-human CD20/human transferrin receptor antibodies and methods of use |
WO2017055542A1 (en) | 2015-10-02 | 2017-04-06 | F. Hoffmann-La Roche Ag | Bispecific anti-human cd20/human transferrin receptor antibodies and methods of use |
WO2017062682A2 (en) | 2015-10-06 | 2017-04-13 | Genentech, Inc. | Method for treating multiple sclerosis |
WO2017066714A1 (en) | 2015-10-16 | 2017-04-20 | Compugen Ltd. | Anti-vsig1 antibodies and drug conjugates |
US10604577B2 (en) | 2015-10-22 | 2020-03-31 | Allakos Inc. | Methods and compositions for treating systemic mastocytosis |
WO2017070561A1 (en) | 2015-10-23 | 2017-04-27 | Pfizer Inc. | Anti-il-2 antibodies and compositions and uses thereof |
US9963500B2 (en) | 2015-10-29 | 2018-05-08 | Merck Sharp & Dohme Corp. | Antibody neutralizing human respiratory syncytial virus |
US11008380B2 (en) | 2015-10-29 | 2021-05-18 | Merck Sharp & Dohme Corp. | Antibody neutralizing human respiratory syncytial virus |
US10358480B2 (en) | 2015-10-29 | 2019-07-23 | Merck Sharp & Dohme Corp. | Antibody neutralizing human respiratory syncytial virus |
US11981726B2 (en) | 2015-10-29 | 2024-05-14 | Merck Sharp & Dohme Llc | Antibody neutralizing human respiratory syncytial virus |
US11566065B2 (en) | 2015-10-29 | 2023-01-31 | Merck Sharp & Dohme Llc | Antibody neutralizing human respiratory syncytial virus |
EP3797797A1 (en) | 2015-10-29 | 2021-03-31 | Novartis AG | Antibody conjugates comprising toll-like receptor agonist |
WO2017072662A1 (en) | 2015-10-29 | 2017-05-04 | Novartis Ag | Antibody conjugates comprising toll-like receptor agonist |
US10072072B2 (en) | 2015-10-29 | 2018-09-11 | Merck Sharp & Dohme Corp. | Antibody neutralizing human respiratory syncytial virus |
WO2017075124A1 (en) | 2015-10-29 | 2017-05-04 | Merck Sharp & Dohme Corp. | Antibody neutralizing human respiratory syncytial virus |
US10323079B2 (en) | 2015-10-29 | 2019-06-18 | Merck Sharp & Dohme Corp. | Antibody neutralizing human respiratory syncytial virus |
WO2017075229A1 (en) | 2015-10-30 | 2017-05-04 | Genentech, Inc. | Hinge modified antibody fragments and methods of making |
EP4036120A1 (en) | 2015-10-30 | 2022-08-03 | F. Hoffmann-La Roche AG | Hinge modified antibody fragments and methods of making |
US10407510B2 (en) | 2015-10-30 | 2019-09-10 | Genentech, Inc. | Anti-factor D antibodies and conjugates |
US10654932B2 (en) | 2015-10-30 | 2020-05-19 | Genentech, Inc. | Anti-factor D antibody variant conjugates and uses thereof |
US10662254B2 (en) | 2015-10-30 | 2020-05-26 | Genentech, Inc. | Hinge modified antibody fragments and methods of making |
US10961313B2 (en) | 2015-10-30 | 2021-03-30 | Genentech, Inc. | Anti-factor D antibody variant conjugates and uses thereof |
US11649293B2 (en) | 2015-11-18 | 2023-05-16 | Chugai Seiyaku Kabushiki Kaisha | Method for enhancing humoral immune response |
US11660340B2 (en) | 2015-11-18 | 2023-05-30 | Chugai Seiyaku Kabushiki Kaisha | Combination therapy using T cell redirection antigen binding molecule against cell having immunosuppressing function |
WO2017087678A2 (en) | 2015-11-19 | 2017-05-26 | Bristol-Myers Squibb Company | Antibodies against glucocorticoid-induced tumor necrosis factor receptor (gitr) and uses thereof |
WO2017095875A1 (en) | 2015-11-30 | 2017-06-08 | Bristol-Myers Squibb Company | Anti human ip-10 antibodies and their uses |
US10836830B2 (en) | 2015-12-02 | 2020-11-17 | Agenus Inc. | Antibodies and methods of use thereof |
US11253590B2 (en) | 2015-12-02 | 2022-02-22 | Stsciences, Inc. | Antibodies specific to glycosylated BTLA (B- and T- lymphocyte attenuator) |
EP3909983A1 (en) | 2015-12-02 | 2021-11-17 | STCube & Co. Inc. | Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof |
US11447557B2 (en) | 2015-12-02 | 2022-09-20 | Agenus Inc. | Antibodies and methods of use thereof |
WO2017096051A1 (en) | 2015-12-02 | 2017-06-08 | Stcube & Co., Inc. | Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof |
WO2017093947A1 (en) | 2015-12-04 | 2017-06-08 | Novartis Ag | Antibody cytokine engrafted compositions and methods of use for immunoregulation |
US11840571B2 (en) | 2015-12-14 | 2023-12-12 | Macrogenics, Inc. | Methods of using bispecific molecules having immunoreactivity with PD-1 and CTLA-4 |
US10954301B2 (en) | 2015-12-14 | 2021-03-23 | Macrogenics, Inc. | Bispecific molecules having immunoreactivity with PD-1 and CTLA-4, and methods of use thereof |
WO2017106129A1 (en) | 2015-12-16 | 2017-06-22 | Merck Sharp & Dohme Corp. | Anti-lag3 antibodies and antigen-binding fragments |
WO2017103895A1 (en) | 2015-12-18 | 2017-06-22 | Novartis Ag | Antibodies targeting cd32b and methods of use thereof |
US11359009B2 (en) | 2015-12-25 | 2022-06-14 | Chugai Seiyaku Kabushiki Kaisha | Anti-myostatin antibodies and methods of use |
US11649262B2 (en) | 2015-12-28 | 2023-05-16 | Chugai Seiyaku Kabushiki Kaisha | Method for promoting efficiency of purification of Fc region-containing polypeptide |
US11505599B2 (en) | 2016-01-14 | 2022-11-22 | Memorial Sloan-Kettering Cancer Center | T cell receptor-like antibodies specific for Foxp3-derived peptides |
WO2017124001A2 (en) | 2016-01-14 | 2017-07-20 | Memorial Sloan-Kettering Cancer Center | T cell receptor-like antibodies specific for foxp3-derived peptides |
WO2017136358A1 (en) | 2016-02-01 | 2017-08-10 | Bioverativ Therapeutics Inc. | Optimized factor viii genes |
EP4137570A1 (en) | 2016-02-01 | 2023-02-22 | Bioverativ Therapeutics Inc. | Optimized factor viii genes |
US11753461B2 (en) | 2016-02-01 | 2023-09-12 | Bioverativ Therapeutics Inc. | Optimized factor VIII genes |
WO2017136558A1 (en) | 2016-02-04 | 2017-08-10 | Curis, Inc. | Mutant smoothened and methods of using the same |
US10899836B2 (en) | 2016-02-12 | 2021-01-26 | Janssen Pharmaceutica Nv | Method of identifying anti-VISTA antibodies |
US11987630B2 (en) | 2016-02-12 | 2024-05-21 | Janssen Pharmaceutica Nv | Anti-vista antibodies and fragments, uses thereof, and methods of identifying same |
WO2017141208A1 (en) | 2016-02-17 | 2017-08-24 | Novartis Ag | Tgfbeta 2 antibodies |
WO2017152085A1 (en) | 2016-03-04 | 2017-09-08 | Bristol-Myers Squibb Company | Combination therapy with anti-cd73 antibodies |
JP2019518712A (en) * | 2016-03-14 | 2019-07-04 | ウニヴァーシテテット イ オスロ | Modified immunoglobulin with altered FcRn |
US11072666B2 (en) | 2016-03-14 | 2021-07-27 | Chugai Seiyaku Kabushiki Kaisha | Cell injury inducing therapeutic drug for use in cancer therapy |
WO2017159699A1 (en) | 2016-03-15 | 2017-09-21 | Chugai Seiyaku Kabushiki Kaisha | Methods of treating cancers using pd-1 axis binding antagonists and anti-gpc3 antibodies |
WO2017157895A1 (en) | 2016-03-15 | 2017-09-21 | Innate Pharma | Anti-mica antibodies |
EP4112641A1 (en) | 2016-03-15 | 2023-01-04 | Chugai Seiyaku Kabushiki Kaisha | Methods of treating cancers using pd-1 axis binding antagonists and anti-gpc3 antibodies |
WO2017161173A1 (en) | 2016-03-16 | 2017-09-21 | Merrimack Pharmaceuticals, Inc. | Engineered trail for cancer therapy |
WO2017162678A1 (en) | 2016-03-22 | 2017-09-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Humanized anti-claudin-1 antibodies and uses thereof |
US10745487B2 (en) | 2016-03-22 | 2020-08-18 | Bionomics Limited | Method of treating cancer by administering an anti-LGR5 monoclonal antibody |
WO2017172771A2 (en) | 2016-03-29 | 2017-10-05 | Janssen Biotech, Inc. | Method of treating psoriasis with increased interval dosing of anti-il12/23 antibody |
US10882914B2 (en) | 2016-04-15 | 2021-01-05 | Alpine Immune Sciences, Inc. | ICOS ligand variant immunomodulatory proteins and uses thereof |
US11525000B2 (en) | 2016-04-15 | 2022-12-13 | Immunext, Inc. | Anti-human VISTA antibodies and use thereof |
US11479609B2 (en) | 2016-04-15 | 2022-10-25 | Alpine Immune Sciences, Inc. | CD80 variant immunomodulatory proteins and uses thereof |
US11498967B2 (en) | 2016-04-15 | 2022-11-15 | Alpine Immune Sciences, Inc. | CD80 variant immunomodulatory proteins and uses thereof |
US11359022B2 (en) | 2016-04-15 | 2022-06-14 | Alpine Immune Sciences, Inc. | CD80 variant immunomodulatory proteins and uses thereof |
US11078282B2 (en) | 2016-04-15 | 2021-08-03 | Alpine Immune Sciences, Inc. | CD80 variant immunomodulatory proteins and uses thereof |
US11591400B2 (en) | 2016-04-15 | 2023-02-28 | Macrogenics, Inc. | B7-H3 directed antibody drug conjugates |
US11603403B2 (en) | 2016-04-15 | 2023-03-14 | Immunext, Inc. | Anti-human vista antibodies and use thereof |
US11603402B2 (en) | 2016-04-15 | 2023-03-14 | Immunext, Inc. | Anti-human vista antibodies and use thereof |
WO2017181139A2 (en) | 2016-04-15 | 2017-10-19 | Michael Molloy | Anti-human vista antibodies and use thereof |
US11649283B2 (en) | 2016-04-15 | 2023-05-16 | Immunext, Inc. | Anti-human vista antibodies and use thereof |
WO2017181152A2 (en) | 2016-04-15 | 2017-10-19 | Alpine Immune Sciences, Inc. | Cd80 variant immunomodulatory proteins and uses thereof |
US10961311B2 (en) | 2016-04-15 | 2021-03-30 | Macrogenics, Inc. | B7-H3 binding molecules, antibody drug conjugates thereof and methods of use thereof |
WO2017181148A2 (en) | 2016-04-15 | 2017-10-19 | Alpine Immune Sciences, Inc. | Icos ligand variant immunomodulatory proteins and uses thereof |
WO2017184562A1 (en) | 2016-04-20 | 2017-10-26 | Merck Sharp & Dohme Corp. | Cmv neutralizing antigen binding proteins |
US10934359B2 (en) | 2016-04-21 | 2021-03-02 | Abbvie Stemcentrx Llc | Anti-BMPR1B antibodies and methods of use |
US11208632B2 (en) | 2016-04-26 | 2021-12-28 | R.P. Scherer Technologies, Llc | Antibody conjugates and methods of making and using the same |
US11788066B2 (en) | 2016-04-26 | 2023-10-17 | R.P. Scherer Technologies, Llc | Antibody conjugates and methods of making and using the same |
WO2017189724A1 (en) | 2016-04-27 | 2017-11-02 | Novartis Ag | Antibodies against growth differentiation factor 15 and uses thereof |
WO2017196663A1 (en) | 2016-05-09 | 2017-11-16 | Bristol-Myers Squibb Company | Tl1a antibodies and uses thereof |
US10968279B2 (en) | 2016-05-09 | 2021-04-06 | Bristol-Myers Squibb Company | TL1A antibodies and uses thereof |
US11767364B2 (en) | 2016-05-09 | 2023-09-26 | Bristol-Myers Squibb Company | TL1A antibodies and methods of treatment |
WO2017203450A1 (en) | 2016-05-25 | 2017-11-30 | Novartis Ag | Reversal binding agents for anti-factor xi/xia antibodies and uses thereof |
US10647780B2 (en) | 2016-05-25 | 2020-05-12 | Novartis Ag | Reversal binding agents for anti-factor XI/XIa antibodies and uses thereof |
WO2017205721A1 (en) | 2016-05-27 | 2017-11-30 | Agenus Inc. | Anti-tim-3 antibodies and methods of use thereof |
WO2017216724A1 (en) | 2016-06-15 | 2017-12-21 | Novartis Ag | Methods for treating disease using inhibitors of bone morphogenetic protein 6 (bmp6) |
KR20220038530A (en) | 2016-06-17 | 2022-03-28 | 추가이 세이야쿠 가부시키가이샤 | Anti-myostatin antibodies and methods of use |
KR20210118979A (en) | 2016-06-17 | 2021-10-01 | 추가이 세이야쿠 가부시키가이샤 | Anti-myostatin antibodies and methods of use |
KR20220143961A (en) | 2016-06-17 | 2022-10-25 | 추가이 세이야쿠 가부시키가이샤 | Anti-myostatin antibodies and methods of use |
KR20190009272A (en) | 2016-06-17 | 2019-01-28 | 추가이 세이야쿠 가부시키가이샤 | Anti-myostatin antibodies and methods of use |
WO2018005954A2 (en) | 2016-07-01 | 2018-01-04 | Resolve Therapeutics, Llc | Optimized binuclease fusions and methods |
WO2018013818A2 (en) | 2016-07-14 | 2018-01-18 | Bristol-Myers Squibb Company | Antibodies against tim3 and uses thereof |
US11591392B2 (en) | 2016-07-14 | 2023-02-28 | Bristol-Myers Squibb Company | Antibodies against TIM3 and uses thereof |
US10077306B2 (en) | 2016-07-14 | 2018-09-18 | Bristol-Myers Squibb Company | Antibodies against TIM3 and uses thereof |
US10533052B2 (en) | 2016-07-14 | 2020-01-14 | Bristol-Myers Squibb Company | Antibodies against TIM3 and uses thereof |
US11618784B2 (en) | 2016-07-19 | 2023-04-04 | Teva Pharmaceuticals Australia Pty Ltd. | Anti-CD47 combination therapy |
WO2018022946A1 (en) | 2016-07-28 | 2018-02-01 | Alpine Immune Sciences, Inc. | Cd155 variant immunomodulatory proteins and uses thereof |
WO2018022945A1 (en) | 2016-07-28 | 2018-02-01 | Alpine Immune Sciences, Inc. | Cd112 variant immunomodulatory proteins and uses thereof |
US11834490B2 (en) | 2016-07-28 | 2023-12-05 | Alpine Immune Sciences, Inc. | CD112 variant immunomodulatory proteins and uses thereof |
US11471488B2 (en) | 2016-07-28 | 2022-10-18 | Alpine Immune Sciences, Inc. | CD155 variant immunomodulatory proteins and uses thereof |
WO2018020476A1 (en) | 2016-07-29 | 2018-02-01 | Aduro Biotech Holdings, Europe B.V. | Anti-pd-1 antibodies |
WO2018020000A1 (en) | 2016-07-29 | 2018-02-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antibodies targeting tumor associated macrophages and uses thereof |
US11858980B2 (en) | 2016-08-02 | 2024-01-02 | Visterra, Inc. | Engineered polypeptides and uses thereof |
WO2018025178A1 (en) | 2016-08-02 | 2018-02-08 | Aduro Biotech Holdings, Europe B.V. | Antibodies against human ctla-4 |
US10808030B2 (en) | 2016-08-02 | 2020-10-20 | Aduro Biotech Holdings, Europe B.V. | Anti-HCTLA-4 antibodies |
US11649285B2 (en) | 2016-08-03 | 2023-05-16 | Bio-Techne Corporation | Identification of VSIG3/VISTA as a novel immune checkpoint and use thereof for immunotherapy |
US11053308B2 (en) | 2016-08-05 | 2021-07-06 | Chugai Seiyaku Kabushiki Kaisha | Method for treating IL-8-related diseases |
US11780912B2 (en) | 2016-08-05 | 2023-10-10 | Chugai Seiyaku Kabushiki Kaisha | Composition for prophylaxis or treatment of IL-8 related diseases |
WO2018027203A1 (en) | 2016-08-05 | 2018-02-08 | Allakos, Inc. | Anti-siglec-7 antibodies for the treatment of cancer |
WO2018033798A1 (en) | 2016-08-17 | 2018-02-22 | Compugen Ltd. | Anti-tigit antibodies, anti-pvrig antibodies and combinations thereof |
EP3617232A1 (en) | 2016-08-17 | 2020-03-04 | Compugen Ltd. | Anti-tigit antibodies, anti-pvrig antibodies and combinations thereof |
WO2018044970A1 (en) | 2016-08-31 | 2018-03-08 | University Of Rochester | Human monoclonal antibodies to human endogenous retrovirus k envelope (herv-k) and uses thereof |
WO2018045379A1 (en) | 2016-09-02 | 2018-03-08 | Dana-Farber Cancer Institute, Inc. | Composition and methods of treating b cell disorders |
US10870694B2 (en) | 2016-09-02 | 2020-12-22 | Dana Farber Cancer Institute, Inc. | Composition and methods of treating B cell disorders |
WO2018053032A1 (en) | 2016-09-13 | 2018-03-22 | Humanigen, Inc. | Epha3 antibodies for the treatment of pulmonary fibrosis |
US10604561B2 (en) | 2016-09-16 | 2020-03-31 | Chugai Seiyaku Kabushiki Kaisha | Anti-dengue virus antibodies, polypeptides containing variant Fc regions, and methods of use |
US10844113B2 (en) | 2016-09-16 | 2020-11-24 | Chugai Seiyaku Kabushiki Kaisha | Anti-dengue virus antibodies, polypeptides containing variant Fc regions, and methods of use |
US11780908B2 (en) | 2016-09-16 | 2023-10-10 | Chugai Seiyaku Kabushiki Kaisha | Anti-dengue virus antibodies, polypeptides containing variant FC regions, and methods of use |
WO2018052818A1 (en) | 2016-09-16 | 2018-03-22 | Henlix, Inc. | Anti-pd-1 antibodies |
EP4339615A2 (en) | 2016-09-16 | 2024-03-20 | Shanghai Henlius Biotech, Inc. | Anti-pd-1 antibodies |
US10751414B2 (en) | 2016-09-19 | 2020-08-25 | Celgene Corporation | Methods of treating psoriasis using PD-1 binding antibodies |
US10766958B2 (en) | 2016-09-19 | 2020-09-08 | Celgene Corporation | Methods of treating vitiligo using PD-1 binding antibodies |
EP4360714A2 (en) | 2016-09-21 | 2024-05-01 | Nextcure, Inc. | Antibodies for siglec-15 and methods of use thereof |
WO2018057735A1 (en) | 2016-09-21 | 2018-03-29 | Nextcure, Inc. | Antibodies for siglec-15 and methods of use thereof |
WO2018058022A1 (en) | 2016-09-26 | 2018-03-29 | Merck Sharp & Dohme Corp. | Anti-cd27 antibodies |
WO2018064436A1 (en) | 2016-09-30 | 2018-04-05 | Janssen Biotech, Inc. | Safe and effective method of treating psoriasis with anti-il23 specific antibody |
US10844119B2 (en) | 2016-10-11 | 2020-11-24 | Agenus Inc. | Anti-LAG-3 antibodies and methods of use thereof |
WO2018071500A1 (en) | 2016-10-11 | 2018-04-19 | Agenus Inc. | Anti-lag-3 antibodies and methods of use thereof |
US11993651B2 (en) | 2016-10-11 | 2024-05-28 | Agenus Inc. | Anti-lag-3 antibodies and methods of use thereof |
US10882908B2 (en) | 2016-10-11 | 2021-01-05 | Agenus Inc. | Anti-LAG-3 antibodies and methods of use thereof |
WO2018073363A1 (en) | 2016-10-21 | 2018-04-26 | Innate Pharma | Treatment with anti-kir3dl2 agents |
US11667890B2 (en) | 2016-10-31 | 2023-06-06 | Iovance Biotherapeutics, Inc. | Engineered artificial antigen presenting cells for tumor infiltrating lymphocyte expansion |
US10415015B2 (en) | 2016-10-31 | 2019-09-17 | Iovance Biotherapeutics, Inc. | Engineered artificial antigen presenting cells for tumor infiltrating lymphocyte expansion |
US11124577B2 (en) | 2016-11-02 | 2021-09-21 | Engmab Sàrl | Bispecific antibody against BCMA and CD3 and an immunological drug for combined use in treating multiple myeloma |
WO2018083204A1 (en) | 2016-11-02 | 2018-05-11 | Engmab Sàrl | Bispecific antibody against bcma and cd3 and an immunological drug for combined use in treating multiple myeloma |
US11359028B2 (en) | 2016-11-09 | 2022-06-14 | Agenus Inc. | Anti-OX40 antibodies and anti-GITR antibodies |
WO2018087720A1 (en) | 2016-11-14 | 2018-05-17 | Novartis Ag | Compositions, methods, and therapeutic uses related to fusogenic protein minion |
WO2018093841A1 (en) | 2016-11-16 | 2018-05-24 | Janssen Biotech, Inc. | Method of treating psoriasis with anti-il-23 specific antibody |
WO2018098363A2 (en) | 2016-11-23 | 2018-05-31 | Bioverativ Therapeutics Inc. | Bispecific antibodies binding to coagulation factor ix and coagulation factor x |
WO2018102760A1 (en) | 2016-12-02 | 2018-06-07 | Bioverativ Therapeutics Inc. | Methods of inducing immune tolerance to clotting factors |
WO2018102743A1 (en) | 2016-12-02 | 2018-06-07 | Bioverativ Therapeutics Inc. | Methods of treating hemophilic arthropathy using chimeric clotting factors |
WO2018104893A1 (en) | 2016-12-06 | 2018-06-14 | Glaxosmithkline Intellectual Property Development Limited | Alpha4-beta7 antibodies with incrased fcrn binding and/or half-life |
EP4289484A2 (en) | 2016-12-07 | 2023-12-13 | Agenus Inc. | Anti-ctla-4 antibodies and methods of use thereof |
WO2018106862A1 (en) | 2016-12-07 | 2018-06-14 | Agenus Inc. | Anti-ctla-4 antibodies and methods of use thereof |
WO2018106864A1 (en) | 2016-12-07 | 2018-06-14 | Agenus Inc. | Antibodies and methods of use thereof |
US11267883B2 (en) | 2016-12-21 | 2022-03-08 | Cephalon, Inc. | Antibodies that specifically bind to human IL-15 and uses thereof |
WO2018115262A1 (en) | 2016-12-23 | 2018-06-28 | Innate Pharma | Heterodimeric antigen binding proteins |
US11168147B2 (en) | 2016-12-23 | 2021-11-09 | Novartis Ag | Factor XI antibodies and methods of use |
WO2018116255A1 (en) | 2016-12-23 | 2018-06-28 | Novartis Ag | Factor xi antibodies and methods of use |
US12012464B2 (en) | 2016-12-23 | 2024-06-18 | Novartis Ag | Factor XI antibodies and methods of use |
WO2018129029A1 (en) | 2017-01-04 | 2018-07-12 | Immunogen, Inc. | Met antibodies and immunoconjugates and uses thereof |
WO2018129336A1 (en) | 2017-01-06 | 2018-07-12 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes with potassium channel agonists and therapeutic uses thereof |
WO2018129332A1 (en) | 2017-01-06 | 2018-07-12 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes (tils) with tumor necrosis factor receptor superfamily (tnfrsf) agonists and therapeutic combinations of tils and tnfrsf agonists |
US11274157B2 (en) | 2017-01-12 | 2022-03-15 | Eureka Therapeutics, Inc. | Constructs targeting histone H3 peptide/MHC complexes and uses thereof |
WO2018146594A1 (en) | 2017-02-08 | 2018-08-16 | Novartis Ag | Fgf21 mimetic antibodies and uses thereof |
WO2018151821A1 (en) | 2017-02-17 | 2018-08-23 | Bristol-Myers Squibb Company | Antibodies to alpha-synuclein and uses thereof |
US11827695B2 (en) | 2017-02-17 | 2023-11-28 | Bristol-Myers Squibb Company | Antibodies to alpha-synuclein and uses thereof |
US11142570B2 (en) | 2017-02-17 | 2021-10-12 | Bristol-Myers Squibb Company | Antibodies to alpha-synuclein and uses thereof |
WO2018160536A1 (en) | 2017-02-28 | 2018-09-07 | Bristol-Myers Squibb Company | Use of anti-ctla-4 antibodies with enhanced adcc to enhance immune response to a vaccine |
WO2018158398A1 (en) | 2017-03-02 | 2018-09-07 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antibodies having specificity to nectin-4 and uses thereof |
US11117950B2 (en) | 2017-03-16 | 2021-09-14 | Alpine Immune Sciences, Inc. | CD80 variant immunomodulatory proteins and uses thereof |
US11117948B2 (en) | 2017-03-16 | 2021-09-14 | Alpine Immune Sciences, Inc. | CD80 variant immunomodulatory proteins and uses thereof |
US11096988B2 (en) | 2017-03-16 | 2021-08-24 | Alpine Immune Sciences, Inc. | CD80 variant immunomodulatory proteins and uses thereof |
US11230588B2 (en) | 2017-03-16 | 2022-01-25 | Alpine Immune Sciences, Inc. | CD80 variant immunomodulatory proteins and uses thereof |
US11732022B2 (en) | 2017-03-16 | 2023-08-22 | Alpine Immune Sciences, Inc. | PD-L2 variant immunomodulatory proteins and uses thereof |
WO2018170023A1 (en) | 2017-03-16 | 2018-09-20 | Alpine Immune Sciences, Inc. | Pd-l2 variant immunomodulatory proteins and uses thereof |
US11639375B2 (en) | 2017-03-16 | 2023-05-02 | Alpine Immune Sciences, Inc. | CD80 variant immunomodulatory proteins and uses thereof |
WO2018170021A1 (en) | 2017-03-16 | 2018-09-20 | Alpine Immune Sciences, Inc. | Pd-l1 variant immunomodulatory proteins and uses thereof |
WO2018170026A2 (en) | 2017-03-16 | 2018-09-20 | Alpine Immune Sciences, Inc. | Cd80 variant immunomodulatory proteins and uses thereof |
US11117949B2 (en) | 2017-03-16 | 2021-09-14 | Alpine Immune Sciences, Inc. | CD80 variant immunomodulatory proteins and uses thereof |
EP4306537A2 (en) | 2017-03-16 | 2024-01-17 | Alpine Immune Sciences, Inc. | Pd-l1 variant immunomodulatory proteins and uses thereof |
WO2018175460A1 (en) | 2017-03-24 | 2018-09-27 | Novartis Ag | Methods for preventing and treating heart disease |
WO2018185618A1 (en) | 2017-04-03 | 2018-10-11 | Novartis Ag | Anti-cdh6 antibody drug conjugates and anti-gitr antibody combinations and methods of treatment |
WO2018187518A1 (en) | 2017-04-07 | 2018-10-11 | Merck Sharp & Dohme Corp. | Anti-ilt4 antibodies and antigen-binding fragments |
WO2018191502A2 (en) | 2017-04-13 | 2018-10-18 | Agenus Inc. | Anti-cd137 antibodies and methods of use thereof |
WO2018189381A1 (en) | 2017-04-14 | 2018-10-18 | Gamamabs Pharma | Amhrii-binding compounds for preventing or treating lung cancers |
WO2018189379A1 (en) | 2017-04-14 | 2018-10-18 | Gamamabs Pharma | Amhrii-binding compounds for preventing or treating cancers |
WO2018195338A1 (en) | 2017-04-20 | 2018-10-25 | Atyr Pharma, Inc. | Compositions and methods for treating lung inflammation |
US11447564B2 (en) | 2017-04-26 | 2022-09-20 | Eureka Therapeutics, Inc. | Constructs specifically recognizing glypican 3 and uses thereof |
WO2018198091A1 (en) | 2017-04-28 | 2018-11-01 | Novartis Ag | Antibody conjugates comprising toll-like receptor agonist and combination therapies |
WO2018204363A1 (en) | 2017-05-01 | 2018-11-08 | Agenus Inc. | Anti-tigit antibodies and methods of use thereof |
EP4275698A2 (en) | 2017-05-01 | 2023-11-15 | Agenus Inc. | Anti-tigit antibodies and methods of use thereof |
US11203638B2 (en) | 2017-05-05 | 2021-12-21 | Allakos Inc. | Methods and compositions for treating perennial allergic conjunctivitis and keratoconjunctivitis |
WO2018209115A1 (en) | 2017-05-10 | 2018-11-15 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof |
WO2018213097A1 (en) | 2017-05-15 | 2018-11-22 | University Of Rochester | Broadly neutralizing anti-influenza monoclonal antibody and uses thereof |
WO2018215936A1 (en) | 2017-05-24 | 2018-11-29 | Novartis Ag | Antibody-cytokine engrafted proteins and methods of use in the treatment of cancer |
WO2018215935A1 (en) | 2017-05-24 | 2018-11-29 | Novartis Ag | Antibody-cytokine engrafted proteins and methods of use for immune related disorders |
WO2018215938A1 (en) | 2017-05-24 | 2018-11-29 | Novartis Ag | Antibody-cytokine engrafted proteins and methods of use |
WO2018215937A1 (en) | 2017-05-24 | 2018-11-29 | Novartis Ag | Interleukin-7 antibody cytokine engrafted proteins and methods of use in the treatment of cancer |
EP4098662A1 (en) | 2017-05-25 | 2022-12-07 | Bristol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
WO2018218056A1 (en) | 2017-05-25 | 2018-11-29 | Birstol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
WO2018222689A1 (en) | 2017-05-31 | 2018-12-06 | Stcube & Co., Inc. | Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof |
WO2018222685A1 (en) | 2017-05-31 | 2018-12-06 | Stcube & Co., Inc. | Methods of treating cancer using antibodies and molecules that immunospecifically bind to btn1a1 |
WO2018220446A1 (en) | 2017-06-01 | 2018-12-06 | Compugen Ltd. | Triple combination antibody therapies |
WO2018226671A1 (en) | 2017-06-06 | 2018-12-13 | Stcube & Co., Inc. | Methods of treating cancer using antibodies and molecules that bind to btn1a1 or btn1a1-ligands |
US11542331B2 (en) | 2017-06-06 | 2023-01-03 | Stcube & Co., Inc. | Methods of treating cancer using antibodies and molecules that bind to BTN1A1 or BTN1A1-ligands |
WO2018229612A1 (en) | 2017-06-12 | 2018-12-20 | Novartis Ag | Method of manufacturing bispecific antibodies, bispecific antibodies and therapeutic use of such antibodies |
WO2018229706A1 (en) | 2017-06-16 | 2018-12-20 | Novartis Ag | Combination therapy for the treatment of cancer |
WO2018229715A1 (en) | 2017-06-16 | 2018-12-20 | Novartis Ag | Compositions comprising anti-cd32b antibodies and methods of use thereof |
WO2019003104A1 (en) | 2017-06-28 | 2019-01-03 | Novartis Ag | Methods for preventing and treating urinary incontinence |
WO2019032898A1 (en) | 2017-08-09 | 2019-02-14 | Bioverativ Therapeutics Inc. | Nucleic acid molecules and uses thereof |
WO2019040674A1 (en) | 2017-08-22 | 2019-02-28 | Sanabio, Llc | Soluble interferon receptors and uses thereof |
US11306144B2 (en) | 2017-08-25 | 2022-04-19 | Five Prime Therapeutics, Inc. | B7-H4 antibodies and methods of use thereof |
WO2019040780A1 (en) | 2017-08-25 | 2019-02-28 | Five Prime Therapeutics Inc. | B7-h4 antibodies and methods of use thereof |
US11814431B2 (en) | 2017-08-25 | 2023-11-14 | Five Prime Therapeutics, Inc. | B7-H4 antibodies and methods of use thereof |
WO2019057567A1 (en) | 2017-09-19 | 2019-03-28 | Tillotts Pharma Ag | Antibody variants |
EP3456737A1 (en) | 2017-09-19 | 2019-03-20 | Tillotts Pharma Ag | Antibody variants |
EP3456736A1 (en) | 2017-09-19 | 2019-03-20 | Tillotts Pharma Ag | Antibody variants |
WO2019057565A1 (en) | 2017-09-19 | 2019-03-28 | Tillotts Pharma Ag | Antibody variants |
WO2019059411A1 (en) | 2017-09-20 | 2019-03-28 | Chugai Seiyaku Kabushiki Kaisha | Dosage regimen for combination therapy using pd-1 axis binding antagonists and gpc3 targeting agent |
WO2019058345A2 (en) | 2017-09-25 | 2019-03-28 | Janssen Biotech, Inc. | Safe and effective method of treating lupus with anti-il12/il23 antibody |
WO2019075090A1 (en) | 2017-10-10 | 2019-04-18 | Tilos Therapeutics, Inc. | Anti-lap antibodies and uses thereof |
WO2019074983A1 (en) | 2017-10-10 | 2019-04-18 | Alpine Immune Sciences, Inc. | Ctla-4 variant immunomodulatory proteins and uses thereof |
US11753458B2 (en) | 2017-10-10 | 2023-09-12 | Alpine Immune Sciences, Inc. | CTLA-4 variant immunomodulatory proteins and uses thereof |
EP4219540A2 (en) | 2017-10-10 | 2023-08-02 | Alpine Immune Sciences, Inc. | Ctla-4 variant immunomodulatory proteins and uses thereof |
US11230601B2 (en) | 2017-10-10 | 2022-01-25 | Tilos Therapeutics, Inc. | Methods of using anti-lap antibodies |
US11859010B2 (en) | 2017-10-14 | 2024-01-02 | Cytomx Therapeutics, Inc. | Antibodies, activatable antibodies, bispecific antibodies, and bispecific activatable antibodies and methods of use thereof |
US11472889B2 (en) | 2017-10-14 | 2022-10-18 | Cytomx Therapeutics, Inc. | Antibodies, activatable antibodies, bispecific antibodies, and bispecific activatable antibodies and methods of use thereof |
US11613566B2 (en) | 2017-10-18 | 2023-03-28 | Alpine Immune Sciences, Inc. | Variant ICOS ligand immunomodulatory proteins and related compositions and methods |
WO2019079520A2 (en) | 2017-10-18 | 2019-04-25 | Alpine Immune Sciences, Inc. | Variant icos ligand immunomodulatory proteins and related compositions and methods |
WO2019081983A1 (en) | 2017-10-25 | 2019-05-02 | Novartis Ag | Antibodies targeting cd32b and methods of use thereof |
WO2019093342A1 (en) | 2017-11-08 | 2019-05-16 | 協和発酵キリン株式会社 | BISPECIFIC ANTIBODY WHICH BINDS TO CD40 AND EpCAM |
WO2019101695A1 (en) | 2017-11-21 | 2019-05-31 | Innate Pharma | Multispecific antigen binding proteins |
WO2019102353A1 (en) | 2017-11-22 | 2019-05-31 | Novartis Ag | Reversal binding agents for anti-factor xi/xia antibodies and uses thereof |
WO2019103857A1 (en) | 2017-11-22 | 2019-05-31 | Iovance Biotherapeutics, Inc. | Expansion of peripheral blood lymphocytes (pbls) from peripheral blood |
WO2019106578A2 (en) | 2017-12-01 | 2019-06-06 | Novartis Ag | Polyomavirus neutralizing antibodies |
US11952422B2 (en) | 2017-12-05 | 2024-04-09 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule comprising altered antibody variable region binding CD3 and CD137 |
WO2019110823A1 (en) | 2017-12-08 | 2019-06-13 | Argenx Bvba | Use of fcrn antagonists for treatment of generalized myasthenia gravis |
WO2019118873A2 (en) | 2017-12-15 | 2019-06-20 | Iovance Biotherapeutics, Inc. | Systems and methods for determining the beneficial administration of tumor infiltrating lymphocytes, and methods of use thereof and beneficial administration of tumor infiltrating lymphocytes, and methods of use thereof |
WO2019115791A1 (en) | 2017-12-15 | 2019-06-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Treatment of monogenic diseases with an anti-cd45rc antibody |
EP3498293A1 (en) | 2017-12-15 | 2019-06-19 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Treatment of monogenic diseases with an anti-cd45rc antibody |
WO2019126536A1 (en) | 2017-12-20 | 2019-06-27 | Alexion Pharmaceuticals Inc. | Humanized anti-cd200 antibodies and uses thereof |
WO2019126133A1 (en) | 2017-12-20 | 2019-06-27 | Alexion Pharmaceuticals, Inc. | Liquid formulations of anti-cd200 antibodies |
WO2019129848A1 (en) | 2017-12-29 | 2019-07-04 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Method for purifying antibodies from raw milk |
WO2019136179A1 (en) | 2018-01-03 | 2019-07-11 | Alpine Immune Sciences, Inc. | Multi-domain immunomodulatory proteins and methods of use thereof |
WO2019140229A1 (en) | 2018-01-12 | 2019-07-18 | Bristol-Myers Squibb Company | Antibodies against tim3 and uses thereof |
RU2795592C2 (en) * | 2018-01-26 | 2023-05-05 | Джензим Корпорейшн | Fc OPTIONS WITH INCREASED FcRn BINDING AND PROLONGED HALF-LIFE |
WO2019147973A1 (en) * | 2018-01-26 | 2019-08-01 | Genzyme Corporation | Fc variants with enhanced binding to fcrn and prolonged half-life |
WO2019152642A1 (en) | 2018-02-01 | 2019-08-08 | Merck Sharp & Dohme Corp. | Anti-pd-1/lag3 bispecific antibodies |
WO2019152692A1 (en) | 2018-02-01 | 2019-08-08 | Bioverativ Therapeutics, Inc. | Use of lentiviral vectors expressing factor viii |
US11072658B2 (en) | 2018-02-01 | 2021-07-27 | Merck Sharp & Dohme Corp. | Anti-PD-1/LAG3 bispecific antibodies |
US11787857B2 (en) | 2018-02-02 | 2023-10-17 | Bio-Techne Corporation | Compounds that modulate the interaction of VISTA and VSIG3 and methods of making and using |
WO2019160829A1 (en) | 2018-02-13 | 2019-08-22 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes (tils) with adenosine a2a receptor antagonists and therapeutic combinations of tils and adenosine a2a receptor antagonists |
WO2019169229A1 (en) | 2018-03-01 | 2019-09-06 | Nextcure, Inc. | Klrg1 binding compositions and methods of use thereof |
WO2019168403A2 (en) | 2018-03-02 | 2019-09-06 | Labo Bio-Medical Investments B.V. | Multispecific binding molecules for the prevention, treatment and diagnosis of neurodegenerative disorders |
US11939383B2 (en) | 2018-03-02 | 2024-03-26 | Five Prime Therapeutics, Inc. | B7-H4 antibodies and methods and use thereof |
WO2019171252A1 (en) | 2018-03-05 | 2019-09-12 | Janssen Biotech, Inc. | Methods of treating crohn's disease with anti-il23 specific antibody |
US11485782B2 (en) | 2018-03-14 | 2022-11-01 | Beijing Xuanyi Pharmasciences Co., Ltd. | Anti-claudin 18.2 antibodies |
US11891432B2 (en) | 2018-03-15 | 2024-02-06 | Chugai Seiyaku Kabushiki Kaisha | Anti-dengue virus antibodies having cross-reactivity to Zika virus and methods of use |
WO2019183040A1 (en) | 2018-03-21 | 2019-09-26 | Five Prime Therapeutics, Inc. | ANTIBODIES BINDING TO VISTA AT ACIDIC pH |
US11242393B2 (en) | 2018-03-23 | 2022-02-08 | Bristol-Myers Squibb Company | Antibodies against MICA and/or MICB and uses thereof |
WO2019191295A1 (en) | 2018-03-28 | 2019-10-03 | Bristol-Myers Squibb Company | Interleukin-2/interleukin-2 receptor alpha fusion proteins and methods of use |
WO2019195126A1 (en) | 2018-04-02 | 2019-10-10 | Bristol-Myers Squibb Company | Anti-trem-1 antibodies and uses thereof |
US11155618B2 (en) | 2018-04-02 | 2021-10-26 | Bristol-Myers Squibb Company | Anti-TREM-1 antibodies and uses thereof |
WO2019197428A1 (en) | 2018-04-10 | 2019-10-17 | Inatherys | Antibody-drug conjugates and their uses for the treatment of cancer |
EP3552631A1 (en) | 2018-04-10 | 2019-10-16 | Inatherys | Antibody-drug conjugates and their uses for the treatment of cancer |
US11648317B2 (en) | 2018-04-13 | 2023-05-16 | Genentech, Inc. | Stable anti-CD79B immunoconjugate formulations |
WO2019213384A1 (en) | 2018-05-03 | 2019-11-07 | University Of Rochester | Anti-influenza neuraminidase monoclonal antibodies and uses thereof |
WO2019215701A1 (en) | 2018-05-11 | 2019-11-14 | Janssen Biotech, Inc. | Methods of treating depression using il-23 antibodies |
WO2019218009A1 (en) | 2018-05-16 | 2019-11-21 | Csl Limited | Soluble complement receptor type 1 variants and uses thereof |
WO2019222682A1 (en) | 2018-05-18 | 2019-11-21 | Bioverativ Therapeutics Inc. | Methods of treating hemophilia a |
WO2019229658A1 (en) | 2018-05-30 | 2019-12-05 | Novartis Ag | Entpd2 antibodies, combination therapies, and methods of using the antibodies and combination therapies |
US11932681B2 (en) | 2018-05-31 | 2024-03-19 | Novartis Ag | Hepatitis B antibodies |
WO2019229699A1 (en) | 2018-05-31 | 2019-12-05 | Novartis Ag | Hepatitis b antibodies |
WO2019229701A2 (en) | 2018-06-01 | 2019-12-05 | Novartis Ag | Binding molecules against bcma and uses thereof |
WO2019232484A1 (en) | 2018-06-01 | 2019-12-05 | Compugen Ltd | Anti-pvrig/anti-tigit bispecific antibodies and methods of use |
WO2019236417A1 (en) | 2018-06-04 | 2019-12-12 | Biogen Ma Inc. | Anti-vla-4 antibodies having reduced effector function |
WO2019235426A1 (en) | 2018-06-04 | 2019-12-12 | 中外製薬株式会社 | Antigen-binding molecule showing changed half-life in cytoplasm |
US11332541B2 (en) | 2018-06-09 | 2022-05-17 | Boehringer Ingelheim International Gmbh | Multi-specific binding proteins for cancer treatment |
WO2019241758A1 (en) | 2018-06-15 | 2019-12-19 | Alpine Immune Sciences, Inc. | Pd-1 variant immunomodulatory proteins and uses thereof |
US11993661B2 (en) | 2018-06-18 | 2024-05-28 | Eureka Therapeutics, Inc. | Constructs targeting prostate-specific membrane antigen (PSMA) and uses thereof |
WO2020010117A2 (en) | 2018-07-03 | 2020-01-09 | Bristol-Myers Squibb Company | Fgf21 formulations |
WO2020014132A2 (en) | 2018-07-09 | 2020-01-16 | Five Prime Therapeutics, Inc. | Antibodies binding to ilt4 |
WO2020014306A1 (en) | 2018-07-10 | 2020-01-16 | Immunogen, Inc. | Met antibodies and immunoconjugates and uses thereof |
WO2020014327A2 (en) | 2018-07-11 | 2020-01-16 | Five Prime Therapeutics, Inc. | Antibodies binding to vista at acidic ph |
WO2020016838A2 (en) | 2018-07-18 | 2020-01-23 | Janssen Biotech, Inc. | Sustained response predictors after treatment with anti-il23 specific antibody |
WO2020033863A1 (en) | 2018-08-09 | 2020-02-13 | Bioverativ Therapeutics Inc. | Nucleic acid molecules and uses thereof for non-viral gene therapy |
WO2020096682A2 (en) | 2018-08-31 | 2020-05-14 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients refractory for anti-pd-1 antibody |
EP4378530A2 (en) | 2018-08-31 | 2024-06-05 | Iovance Biotherapeutics, Inc. | Use of tumor infiltrating lymphocytes for treating nsclc patients refractory for anti-pd-1 antibody |
US11590223B2 (en) | 2018-08-31 | 2023-02-28 | Regeneron Pharmaceuticals, Inc. | Dosing strategy that mitigates cytokine release syndrome for therapeutic antibodies |
WO2020053742A2 (en) | 2018-09-10 | 2020-03-19 | Novartis Ag | Anti-hla-hbv peptide antibodies |
WO2020056077A1 (en) | 2018-09-13 | 2020-03-19 | The Board Of Regents Of The University Of Texas System | Novel lilrb4 antibodies and uses thereof |
WO2020061210A1 (en) | 2018-09-18 | 2020-03-26 | Merrimack Pharmaceuticals, Inc. | Anti-tnfr2 antibodies and uses thereof |
WO2020061376A2 (en) | 2018-09-19 | 2020-03-26 | Alpine Immune Sciences, Inc. | Methods and uses of variant cd80 fusion proteins and related constructs |
WO2020065532A1 (en) | 2018-09-24 | 2020-04-02 | Janssen Biotech, Inc. | Safe and effective method of treating ulcerative colitis with anti-il12/il23 antibody |
US11866476B2 (en) | 2018-09-27 | 2024-01-09 | Xilio Development, Inc. | Masked IL-2-Fc fusion polypeptides |
EP4321530A2 (en) | 2018-09-27 | 2024-02-14 | Xilio Development, Inc. | Masked cytokine polypeptides |
KR20210068061A (en) | 2018-09-28 | 2021-06-08 | 추가이 세이야쿠 가부시키가이샤 | Antigen-binding molecule comprising a modified antibody variable region |
KR20210068079A (en) | 2018-09-28 | 2021-06-08 | 추가이 세이야쿠 가부시키가이샤 | antigen binding molecule capable of binding to CD3 and CD137 but not simultaneously |
US11130802B2 (en) | 2018-10-10 | 2021-09-28 | Tilos Therapeutics, Inc. | Anti-lap antibody variants |
WO2020076969A2 (en) | 2018-10-10 | 2020-04-16 | Tilos Therapeutics, Inc. | Anti-lap antibody variants and uses thereof |
WO2020079580A1 (en) | 2018-10-15 | 2020-04-23 | Novartis Ag | Trem2 stabilizing antibodies |
WO2020089437A1 (en) | 2018-10-31 | 2020-05-07 | Engmab Sàrl | Combination therapy |
WO2020089811A1 (en) | 2018-10-31 | 2020-05-07 | Novartis Ag | Dc-sign antibody drug conjugates |
EP4219550A1 (en) | 2018-11-02 | 2023-08-02 | Oklahoma Medical Research Foundation | Monoclonal antibodies to eltd1 and uses thereof |
WO2020096989A1 (en) | 2018-11-05 | 2020-05-14 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients refractory for anti-pd-1 antibody |
WO2020102555A1 (en) | 2018-11-16 | 2020-05-22 | Memorial Sloan Kettering Cancer Center | Antibodies to mucin-16 and methods of use thereof |
WO2020104943A2 (en) | 2018-11-20 | 2020-05-28 | Janssen Biotech, Inc. | Safe and effective method of treating psoriasis with anti-il-23 specific antibody |
WO2020104705A2 (en) | 2018-11-23 | 2020-05-28 | Katholieke Universiteit Leuven | Predicting a treatment response in inflammatory bowel disease |
WO2020112781A1 (en) | 2018-11-28 | 2020-06-04 | Bristol-Myers Squibb Company | Antibodies comprising modified heavy constant regions |
WO2020113141A2 (en) | 2018-11-30 | 2020-06-04 | Alpine Immune Sciences, Inc. | Cd86 variant immunomodulatory proteins and uses thereof |
WO2020115115A1 (en) | 2018-12-05 | 2020-06-11 | Morphosys Ag | Multispecific antigen-binding molecules |
WO2020116560A1 (en) | 2018-12-05 | 2020-06-11 | 株式会社バイカ・セラピュティクス | Modified product of fc domain of antibody |
WO2020118011A1 (en) | 2018-12-06 | 2020-06-11 | Alexion Pharmaceuticals, Inc. | Anti-alk2 antibodies and uses thereof |
WO2020127509A1 (en) | 2018-12-18 | 2020-06-25 | Catapult Therapeutics B.V. | The use of anti-ccr7 mabs for the prevention or treatment of graft-versus-host disease (gvhd) |
WO2020128864A1 (en) | 2018-12-18 | 2020-06-25 | Janssen Biotech, Inc. | Safe and effective method of treating lupus with anti-il12/il23 antibody |
WO2020128863A1 (en) | 2018-12-19 | 2020-06-25 | Novartis Ag | Anti-tnf-alpha antibodies |
WO2020132230A2 (en) | 2018-12-20 | 2020-06-25 | Genentech, Inc. | Modified antibody fcs and methods of use |
WO2020139926A2 (en) | 2018-12-26 | 2020-07-02 | Akrevia Therapeutics Inc. | Anti-ctla4 antibodies and methods of use thereof |
WO2020139920A2 (en) | 2018-12-26 | 2020-07-02 | City Of Hope | Activatable masked anti-ctla4 binding proteins |
WO2020138487A1 (en) | 2018-12-28 | 2020-07-02 | 協和キリン株式会社 | BISPECIFIC ANTIBODY BINDING TO TfR |
WO2020142740A1 (en) | 2019-01-04 | 2020-07-09 | Resolve Therapeutics, Llc | Treatment of sjogren's disease with nuclease fusion proteins |
WO2020148207A1 (en) | 2019-01-14 | 2020-07-23 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Human monoclonal antibodies binding to hla-a2 |
WO2020154293A1 (en) | 2019-01-22 | 2020-07-30 | Bristol-Myers Squibb Company | Antibodies against il-7r alpha subunit and uses thereof |
WO2020154405A2 (en) | 2019-01-22 | 2020-07-30 | Genentech, Inc. | Immunoglobulin a antibodies and methods of production and use |
US11919962B2 (en) | 2019-01-22 | 2024-03-05 | Bristol Myers-Squibb Company | Antibodies against IL-7R alpha subunit and uses thereof |
US11008395B2 (en) | 2019-01-22 | 2021-05-18 | Bristol Myers-Squibb Company | Antibodies against IL-7R alpha subunit and uses thereof |
WO2020152081A1 (en) | 2019-01-22 | 2020-07-30 | Innate Pharma | Treatment of t cell lymphoma |
WO2020152290A1 (en) | 2019-01-23 | 2020-07-30 | Encefa | Cd31 competitors and uses thereof |
WO2020154540A1 (en) | 2019-01-23 | 2020-07-30 | Millennium Pharmaceuticals, Inc. | Anti-cd38 antibodies |
WO2020153467A1 (en) | 2019-01-24 | 2020-07-30 | 中外製薬株式会社 | Novel cancer antigens and antibodies of said antigens |
WO2020180712A1 (en) | 2019-03-01 | 2020-09-10 | Merrimack Pharmaceuticals, Inc. | Anti-tnfr2 antibodies and uses thereof |
WO2020180733A1 (en) | 2019-03-01 | 2020-09-10 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof |
WO2020183418A1 (en) | 2019-03-14 | 2020-09-17 | Janssen Biotech, Inc. | Manufacturing methods for producing anti-il12/il23 antibody compositions |
WO2020188466A1 (en) | 2019-03-18 | 2020-09-24 | Janssen Biotech, Inc. | Method of treating psoriasis in pediatric subjects with anti-il12/il23 antibody |
WO2020189748A1 (en) | 2019-03-19 | 2020-09-24 | 中外製薬株式会社 | Antigen-binding molecule containing antigen-binding domain of which binding activity to antigen is changed depending on mta, and library for obtaining said antigen-binding domain |
WO2020206063A1 (en) | 2019-04-03 | 2020-10-08 | Genzyme Corporation | Anti-alpha beta tcr binding polypeptides with reduced fragmentation |
WO2020208177A1 (en) | 2019-04-11 | 2020-10-15 | Argenx Bvba | ANTI-IgE ANTIBODIES |
WO2020214867A1 (en) | 2019-04-17 | 2020-10-22 | Alpine Immune Sciences, Inc. | Methods and uses of variant icos ligand (icosl) fusion proteins |
WO2020214748A1 (en) | 2019-04-18 | 2020-10-22 | Bristol-Myers Squibb Company | Ipilimumab variants with enhanced specificity for binding at low ph |
WO2020213724A1 (en) | 2019-04-19 | 2020-10-22 | 中外製薬株式会社 | Chimeric receptor recognizing modification site of antibody |
WO2020230901A1 (en) | 2019-05-15 | 2020-11-19 | 協和キリン株式会社 | Bispecific antibody capable of binding to cd40 and gpc3 |
WO2020230899A1 (en) | 2019-05-15 | 2020-11-19 | 協和キリン株式会社 | Bispecific antibody binding to cd40 and fap |
US12030925B2 (en) | 2019-05-17 | 2024-07-09 | Bioverativ Therapeutics Inc. | Methods of treating hemophilia A |
WO2020236841A2 (en) | 2019-05-20 | 2020-11-26 | Novartis Ag | Antibody drug conjugates having linkers comprising hydrophilic groups |
WO2020236795A2 (en) | 2019-05-21 | 2020-11-26 | Novartis Ag | Trispecific binding molecules against bcma and uses thereof |
WO2020236792A1 (en) | 2019-05-21 | 2020-11-26 | Novartis Ag | Cd19 binding molecules and uses thereof |
WO2020236797A1 (en) | 2019-05-21 | 2020-11-26 | Novartis Ag | Variant cd58 domains and uses thereof |
WO2020246563A1 (en) | 2019-06-05 | 2020-12-10 | 中外製薬株式会社 | Antibody cleavage site-binding molecule |
US11591388B2 (en) | 2019-06-07 | 2023-02-28 | argenx BV | Pharmaceutical formulations of FcRn inhibitors suitable for subcutaneous administration |
WO2020250915A1 (en) | 2019-06-10 | 2020-12-17 | 中外製薬株式会社 | Anti-t cell antigen-binding molecule to be used in combination with cytokine inhibitor |
WO2021006328A1 (en) | 2019-07-10 | 2021-01-14 | Chugai Seiyaku Kabushiki Kaisha | Claudin-6 binding molecules and uses thereof |
WO2021005232A1 (en) | 2019-07-11 | 2021-01-14 | Umc Utrecht Holding B.V. | Intranasal administration of neutralising antiviral antibodies |
WO2021010326A1 (en) | 2019-07-12 | 2021-01-21 | 中外製薬株式会社 | Anti-mutation type fgfr3 antibody and use therefor |
WO2021011681A1 (en) | 2019-07-15 | 2021-01-21 | Bristol-Myers Squibb Company | Antibodies against human trem-1 and uses thereof |
WO2021011678A1 (en) | 2019-07-15 | 2021-01-21 | Bristol-Myers Squibb Company | Anti-trem-1 antibodies and uses thereof |
WO2021009263A1 (en) | 2019-07-16 | 2021-01-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antibodies having specificity for cd38 and uses thereof |
WO2021014389A1 (en) | 2019-07-24 | 2021-01-28 | H. Lundbeck A/S | Anti-mglur5 antibodies and uses thereof |
WO2021021605A1 (en) | 2019-07-26 | 2021-02-04 | Vanderbilt University | Human monoclonal antibodies to enterovirus d68 |
WO2021017892A1 (en) | 2019-07-26 | 2021-02-04 | 上海复宏汉霖生物技术股份有限公司 | Method and composition for anti-cd73 antibodies and variants |
WO2021021837A2 (en) | 2019-07-29 | 2021-02-04 | Compugen Ltd. | Anti-pvrig antibodies formulations and uses thereof |
WO2021024133A2 (en) | 2019-08-06 | 2021-02-11 | Glaxosmithkline Intellectual Property Development Limited | Biopharmacuetical compositions and related methods |
WO2021030488A1 (en) | 2019-08-12 | 2021-02-18 | Bienvenue David Leonard | 4-1bb and ox40 binding proteins and related compositions and methods, antibodies against 4-1bb, antibodies against ox40 |
WO2021042019A1 (en) | 2019-08-30 | 2021-03-04 | Agenus Inc. | Anti-cd96 antibodies and methods of use thereof |
WO2021053560A1 (en) | 2019-09-18 | 2021-03-25 | Novartis Ag | Combination therapy with entpd2 and cd73 antibodies |
WO2021053559A1 (en) | 2019-09-18 | 2021-03-25 | Novartis Ag | Entpd2 antibodies, combination therapies, and methods of using the antibodies and combination therapies |
WO2021055698A1 (en) | 2019-09-19 | 2021-03-25 | Bristol-Myers Squibb Company | Antibodies binding to vista at acidic ph |
WO2021062323A1 (en) | 2019-09-26 | 2021-04-01 | Stcube & Co. | Antibodies specific to glycosylated ctla-4 and methods of use thereof |
WO2021067389A1 (en) | 2019-09-30 | 2021-04-08 | Bioverativ Therapeutics Inc. | Lentiviral vector formulations |
WO2021072277A1 (en) | 2019-10-09 | 2021-04-15 | Stcube & Co. | Antibodies specific to glycosylated lag3 and methods of use thereof |
WO2021091605A1 (en) | 2019-11-04 | 2021-05-14 | Compugen Ltd. | Combination therapy with anti-pvrig antibodies formulations and anti-pd-1 antibodies |
WO2021113831A1 (en) | 2019-12-05 | 2021-06-10 | Compugen Ltd. | Anti-pvrig and anti-tigit antibodies for enhanced nk-cell based tumor killing |
WO2021116119A1 (en) | 2019-12-09 | 2021-06-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antibodies having specificity to her4 and uses thereof |
WO2021131021A1 (en) | 2019-12-27 | 2021-07-01 | 中外製薬株式会社 | Anti-ctla-4 antibody and use thereof |
KR20220119433A (en) | 2019-12-27 | 2022-08-29 | 추가이 세이야쿠 가부시키가이샤 | Anti-CTLA-4 antibodies and uses thereof |
KR20240035914A (en) | 2019-12-27 | 2024-03-18 | 추가이 세이야쿠 가부시키가이샤 | Anti-ctla-4 antibody and use thereof |
WO2021140202A1 (en) | 2020-01-08 | 2021-07-15 | argenx BV | Methods for treating pemphigus disorders |
WO2021158938A1 (en) | 2020-02-06 | 2021-08-12 | Bristol-Myers Squibb Company | Il-10 and uses thereof |
WO2021163265A1 (en) | 2020-02-11 | 2021-08-19 | Vanderbilt University | Human monoclonal antibodies to severe acute respiratory syndrome coronavirus 2 (sars-cov- 2) |
WO2021162098A1 (en) | 2020-02-14 | 2021-08-19 | 協和キリン株式会社 | Bispecific antibody that binds to cd3 |
US11879004B2 (en) | 2020-02-28 | 2024-01-23 | Genzyme Corporation | Modified binding polypeptides for optimized drug conjugation |
WO2021174034A1 (en) | 2020-02-28 | 2021-09-02 | Genzyme Corporation | Modified binding polypeptides for optimized drug conjugation |
US11365239B2 (en) | 2020-03-20 | 2022-06-21 | Tsb Therapeutics (Beijing) Co., Ltd. | Anti-SARS-COV-2 antibodies and uses thereof |
WO2021194861A1 (en) | 2020-03-23 | 2021-09-30 | Genentech, Inc. | Biomarkers for predicting response to il-6 antagonist in covid-19 pneumonia |
WO2021194860A1 (en) | 2020-03-23 | 2021-09-30 | Genentech, Inc. | Tocilizumab and remdesivir combination therapy for covid-19 pneumonia |
WO2021194865A1 (en) | 2020-03-23 | 2021-09-30 | Genentech, Inc. | Method for treating pneumonia, including covid-19 pneumonia, with an il6 antagonist |
WO2021195385A1 (en) | 2020-03-26 | 2021-09-30 | Vanderbilt University | HUMAN MONOCLONAL ANTIBODIES TO SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-GoV-2) |
EP4356924A2 (en) | 2020-03-26 | 2024-04-24 | Vanderbilt University | Human monoclonal antibodies to severe acute respiratory syndrome coronavirus 2 (sars-cov-2) |
WO2021195418A1 (en) | 2020-03-26 | 2021-09-30 | Vanderbilt University | Human monoclonal antibodies to severe acute respiratory syndrome coronavirus 2 (sars-cov-2) |
WO2021195513A1 (en) | 2020-03-27 | 2021-09-30 | Novartis Ag | Bispecific combination therapy for treating proliferative diseases and autoimmune disorders |
US11718672B2 (en) | 2020-03-31 | 2023-08-08 | Chugai Seiyaki Kabushiki Kaisha | CD137- and DLL3-targeting multispecific antigen-binding molecules |
WO2021201087A1 (en) | 2020-03-31 | 2021-10-07 | Chugai Seiyaku Kabushiki Kaisha | Method for producing multispecific antigen-binding molecules |
US11274151B2 (en) | 2020-03-31 | 2022-03-15 | Chugai Seiyaku Kabushiki Kaisha | CD3-targeting and DLL3-targeting multispecific antigen-binding molecules and uses thereof |
WO2021202235A1 (en) | 2020-04-01 | 2021-10-07 | University Of Rochester | Monoclonal antibodies against the hemagglutinin (ha) and neuraminidase (na) of influenza h3n2 viruses |
WO2021207449A1 (en) | 2020-04-09 | 2021-10-14 | Merck Sharp & Dohme Corp. | Affinity matured anti-lap antibodies and uses thereof |
WO2021204179A1 (en) | 2020-04-09 | 2021-10-14 | Suzhou Abogen Biosciences Co., Ltd. | Nucleic acid vaccines for coronavirus |
US12030951B2 (en) | 2020-04-17 | 2024-07-09 | Hutchison Medipharma Limited | Anti-OX40 antibody and uses thereof |
WO2021214277A1 (en) | 2020-04-24 | 2021-10-28 | F. Hoffmann-La Roche Ag | Enzyme and pathway modulation with sulfhydryl compounds and their derivatives |
WO2021222181A2 (en) | 2020-04-27 | 2021-11-04 | The Regents Of The University Of California | Isoform-independent antibodies to lipoprotein(a) |
WO2021222935A2 (en) | 2020-04-28 | 2021-11-04 | The Rockefeller University | Neutralizing anti-sars-cov-2 antibodies and methods of use thereof |
US11274140B2 (en) | 2020-05-08 | 2022-03-15 | Alpine Immune Sciences, Inc. | APRIL and BAFF inhibitory immunomodulatory proteins and methods of use thereof |
WO2021226551A1 (en) | 2020-05-08 | 2021-11-11 | Alpine Immune Sciences, Inc. | April and baff inhibitory immunomodulatory proteins and methods of use thereof |
WO2021226553A2 (en) | 2020-05-08 | 2021-11-11 | Alpine Immune Sciences, Inc. | April and baff inhibitory immunomodulatory proteins with and without a t cell inhibitory protein and methods of use thereof |
WO2021228956A1 (en) | 2020-05-12 | 2021-11-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | New method to treat cutaneous t-cell lymphomas and tfh derived lymphomas |
WO2021231732A1 (en) | 2020-05-15 | 2021-11-18 | Bristol-Myers Squibb Company | Antibodies to garp |
WO2021233834A1 (en) | 2020-05-17 | 2021-11-25 | Astrazeneca Uk Limited | Sars-cov-2 antibodies and methods of selecting and using the same |
WO2021234402A2 (en) | 2020-05-21 | 2021-11-25 | Mabsolve Limited | Modified immunoglobulin fc regions |
WO2021234160A2 (en) | 2020-05-22 | 2021-11-25 | Formycon Ag | Ace2 fusion proteins and uses thereof |
WO2021238886A1 (en) | 2020-05-27 | 2021-12-02 | Staidson (Beijing) Biopharmaceuticals Co., Ltd. | Antibodies specifically recognizing nerve growth factor and uses thereof |
WO2021251438A1 (en) | 2020-06-10 | 2021-12-16 | 株式会社バイカ・セラピュティクス | Fusion protein containing erythropoietin polypeptide |
WO2021256555A1 (en) | 2020-06-19 | 2021-12-23 | 中外製薬株式会社 | Anti-t cell antigen-binding molecule for use in combination with angiogenesis inhibitor |
US11702467B2 (en) | 2020-06-25 | 2023-07-18 | Merck Sharp & Dohme Llc | High affinity antibodies targeting tau phosphorylated at serine 413 |
WO2021262791A1 (en) | 2020-06-25 | 2021-12-30 | Merck Sharp & Dohme Corp. | High affinity antibodies targeting tau phosphorylated at serine 413 |
WO2022006153A1 (en) | 2020-06-29 | 2022-01-06 | Resolve Therapeutics, Llc | Treatment of sjogren's syndrome with nuclease fusion proteins |
WO2022025220A1 (en) | 2020-07-31 | 2022-02-03 | 中外製薬株式会社 | Pharmaceutical composition including cell expressing chimeric receptor |
WO2022031978A1 (en) | 2020-08-06 | 2022-02-10 | Bioverativ Usa Inc. | Inflammatory cytokines and fatigue in subject with a complement mediated disease |
WO2022034044A1 (en) | 2020-08-10 | 2022-02-17 | Astrazeneca Uk Limited | Sars-cov-2 antibodies for treatment and prevention of covid-19 |
WO2022040345A1 (en) | 2020-08-18 | 2022-02-24 | Cephalon, Inc. | Anti-par-2 antibodies and methods of use thereof |
US11725052B2 (en) | 2020-08-18 | 2023-08-15 | Cephalon Llc | Anti-PAR-2 antibodies and methods of use thereof |
WO2022047316A1 (en) | 2020-08-28 | 2022-03-03 | Sana Biotechnology, Inc. | Modified anti-viral binding agents |
WO2022045276A1 (en) | 2020-08-28 | 2022-03-03 | 中外製薬株式会社 | Heterodimer fc polypeptide |
WO2022060412A1 (en) | 2020-09-17 | 2022-03-24 | Genentech, Inc. | Results of empacta: a randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of tocilizumab in hospitalized patients with covid-19 pneumonia |
WO2022069940A1 (en) | 2020-09-30 | 2022-04-07 | Compugen Ltd. | Combination therapy with anti-pvrig antibodies formulations, anti-tigit antibodies, and anti-pd-1 antibodies |
WO2022076952A1 (en) | 2020-10-06 | 2022-04-14 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
WO2022076606A1 (en) | 2020-10-06 | 2022-04-14 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
WO2022084915A1 (en) | 2020-10-22 | 2022-04-28 | Janssen Biotech, Inc. | Proteins comprising delta-like ligand 3 (dll3) antigen binding domains and their uses |
WO2022090801A2 (en) | 2020-10-26 | 2022-05-05 | Compugen Ltd. | Pvrl2 and/or pvrig as biomarkers for treatment |
WO2022090469A2 (en) | 2020-10-29 | 2022-05-05 | Formycon Ag | Ace2 fusion proteins and uses thereof |
WO2022098870A1 (en) | 2020-11-04 | 2022-05-12 | The Rockefeller University | Neutralizing anti-sars-cov-2 antibodies |
WO2022097061A1 (en) | 2020-11-06 | 2022-05-12 | Novartis Ag | Anti-cd19 agent and b cell targeting agent combination therapy for treating b cell malignancies |
WO2022097060A1 (en) | 2020-11-06 | 2022-05-12 | Novartis Ag | Cd19 binding molecules and uses thereof |
WO2022119976A1 (en) | 2020-12-01 | 2022-06-09 | Aptevo Research And Development Llc | Heterodimeric psma and cd3-binding bispecific antibodies |
WO2022123307A1 (en) | 2020-12-09 | 2022-06-16 | Takeda Pharmaceutical Company Limited | Compositions of guanylyl cyclase c (gcc) antigen binding agents and methods of use thereof |
WO2022123316A1 (en) | 2020-12-09 | 2022-06-16 | Takeda Pharmaceutical Company Limited | Compositions of guanylyl cyclase c (gcc) antigen binding agents and methods of use thereof |
WO2022125941A1 (en) | 2020-12-11 | 2022-06-16 | Iovance Biotherapeutics, Inc. | Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with braf inhibitors and/or mek inhibitors |
WO2022130182A1 (en) | 2020-12-14 | 2022-06-23 | Novartis Ag | Reversal binding agents for anti-natriuretic peptide receptor 1 (npr1) antibodies and uses thereof |
WO2022133149A1 (en) | 2020-12-17 | 2022-06-23 | Iovance Biotherapeutics, Inc. | Treatment of cancers with tumor infiltrating lymphocytes |
WO2022133140A1 (en) | 2020-12-17 | 2022-06-23 | Iovance Biotherapeutics, Inc. | Treatment with tumor infiltrating lymphocyte therapies in combination with ctla-4 and pd-1 inhibitors |
WO2022147196A2 (en) | 2020-12-31 | 2022-07-07 | Iovance Biotherapeutics, Inc. | Devices and processes for automated production of tumor infiltrating lymphocytes |
WO2022155324A1 (en) | 2021-01-15 | 2022-07-21 | The Rockefeller University | Neutralizing anti-sars-cov-2 antibodies |
WO2022165266A1 (en) | 2021-01-28 | 2022-08-04 | Compugen Ltd. | Anti-pvrig antibodies formulations and uses thereof |
WO2022165275A2 (en) | 2021-01-28 | 2022-08-04 | Compugen Ltd. | Combination therapy with anti-pvrig antibodies formulations and anti-pd-1-antibodies |
WO2022165260A1 (en) | 2021-01-29 | 2022-08-04 | Iovance Biotherapeutics, Inc. | Methods of making modified tumor infiltrating lymphocytes and their use in adoptive cell therapy |
WO2022172085A2 (en) | 2021-02-15 | 2022-08-18 | Takeda Pharmaceutical Company Limited | Cell therapy compositions and methods for modulating tgf-b signaling |
WO2022187270A1 (en) | 2021-03-01 | 2022-09-09 | Xilio Development, Inc. | Combination of ctla4 and pd1/pdl1 antibodies for treating cancer |
WO2022187272A1 (en) | 2021-03-01 | 2022-09-09 | Xilio Development, Inc. | Combination of masked ctla4 and pd1/pdl1 antibodies for treating cancer |
WO2022184854A2 (en) | 2021-03-03 | 2022-09-09 | Formycon Ag | Formulations of ace2 fc fusion proteins |
WO2022187741A2 (en) | 2021-03-05 | 2022-09-09 | Iovance Biotherapeutics, Inc. | Tumor storage and cell culture compositions |
WO2022190034A1 (en) | 2021-03-12 | 2022-09-15 | Janssen Biotech, Inc. | Method of treating psoriatic arthritis patients with inadequate response to tnf therapy with anti-il23 specific antibody |
WO2022190033A1 (en) | 2021-03-12 | 2022-09-15 | Janssen Biotech, Inc. | Safe and effective method of treating psoriatic arthritis with anti-il23 specific antibody |
WO2022198141A1 (en) | 2021-03-19 | 2022-09-22 | Iovance Biotherapeutics, Inc. | Methods for tumor infiltrating lymphocyte (til) expansion related to cd39/cd69 selection and gene knockout in tils |
WO2022204155A1 (en) | 2021-03-23 | 2022-09-29 | Iovance Biotherapeutics, Inc. | Cish gene editing of tumor infiltrating lymphocytes and uses of same in immunotherapy |
WO2022204564A2 (en) | 2021-03-25 | 2022-09-29 | Iovance Biotherapeutics, Inc. | Methods and compositions for t-cell coculture potency assays and use with cell therapy products |
WO2022200525A1 (en) | 2021-03-26 | 2022-09-29 | Innate Pharma | Multispecific proteins comprising an nkp46-binding site, a cancer antgienge binding site fused to a cytokine for nk cell engaging |
WO2022201122A1 (en) | 2021-03-26 | 2022-09-29 | Janssen Biotech, Inc. | Humanized antibodies against paired helical filament tau and uses thereof |
WO2022212645A1 (en) | 2021-03-31 | 2022-10-06 | Bioverativ Usa Inc. | Reducing surgery-associated hemolysis in cold agglutinin disease patients |
WO2022212876A1 (en) | 2021-04-02 | 2022-10-06 | The Regents Of The University Of California | Antibodies against cleaved cdcp1 and uses thereof |
WO2022225981A2 (en) | 2021-04-19 | 2022-10-27 | Iovance Biotherapeutics, Inc. | Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies |
WO2022235867A2 (en) | 2021-05-06 | 2022-11-10 | The Rockefeller University | Neutralizing anti-sars- cov-2 antibodies and methods of use thereof |
WO2022236335A1 (en) | 2021-05-07 | 2022-11-10 | Alpine Immune Sciences, Inc. | Methods of dosing and treatment with a taci-fc fusion immunomodulatory protein |
WO2022245754A1 (en) | 2021-05-17 | 2022-11-24 | Iovance Biotherapeutics, Inc. | Pd-1 gene-edited tumor infiltrating lymphocytes and uses of same in immunotherapy |
WO2022248870A1 (en) | 2021-05-28 | 2022-12-01 | Glaxosmithkline Intellectual Property Development Limited | Combination therapies for treating cancer |
WO2022253756A1 (en) | 2021-06-01 | 2022-12-08 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of b cell depleting agents for the treatment of rheumatic heart disease |
EP4155321A1 (en) | 2021-06-04 | 2023-03-29 | Chugai Seiyaku Kabushiki Kaisha | Anti-ddr2 antibodies and uses thereof |
WO2022258673A1 (en) | 2021-06-09 | 2022-12-15 | Innate Pharma | Multispecific antibodies binding to cd20, nkp46, cd16 and conjugated to il-2 |
WO2022258662A1 (en) | 2021-06-09 | 2022-12-15 | Innate Pharma | Multispecific proteins binding to nkp46, a cytokine receptor, a tumour antigen and cd16a |
WO2022258678A1 (en) | 2021-06-09 | 2022-12-15 | Innate Pharma | Multispecific proteins binding to nkp30, a cytokine receptor, a tumour antigen and cd16a |
WO2022258691A1 (en) | 2021-06-09 | 2022-12-15 | Innate Pharma | Multispecific proteins binding to nkg2d, a cytokine receptor, a tumour antigen and cd16a |
WO2022261417A1 (en) | 2021-06-11 | 2022-12-15 | Genentech, Inc. | Method for treating chronic obstructive pulmonary disease with an st2 antagonist |
WO2022263357A1 (en) | 2021-06-14 | 2022-12-22 | Argenx Iip Bv | Anti-il-9 antibodies and methods of use thereof |
WO2022269451A1 (en) | 2021-06-22 | 2022-12-29 | Novartis Ag | Bispecific antibodies for use in treatment of hidradenitis suppurativa |
KR20240024255A (en) | 2021-06-25 | 2024-02-23 | 추가이 세이야쿠 가부시키가이샤 | Use of anti-CTLA-4 antibodies |
KR20240024213A (en) | 2021-06-25 | 2024-02-23 | 추가이 세이야쿠 가부시키가이샤 | Anti-CTLA-4 antibody |
WO2023275621A1 (en) | 2021-07-01 | 2023-01-05 | Compugen Ltd. | Anti-tigit and anti-pvrig in monotherapy and combination treatments |
WO2023283611A1 (en) | 2021-07-08 | 2023-01-12 | Staidson Biopharma Inc. | Antibodies specifically recognizing tnfr2 and uses thereof |
WO2023281466A1 (en) | 2021-07-09 | 2023-01-12 | Janssen Biotech, Inc. | Manufacturing methods for producing anti-il12/il23 antibody compositions |
WO2023284714A1 (en) | 2021-07-14 | 2023-01-19 | 舒泰神(北京)生物制药股份有限公司 | Antibody that specifically recognizes cd40 and application thereof |
WO2023004074A2 (en) | 2021-07-22 | 2023-01-26 | Iovance Biotherapeutics, Inc. | Method for cryopreservation of solid tumor fragments |
WO2023010060A2 (en) | 2021-07-27 | 2023-02-02 | Novab, Inc. | Engineered vlrb antibodies with immune effector functions |
WO2023009716A1 (en) | 2021-07-28 | 2023-02-02 | Iovance Biotherapeutics, Inc. | Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with kras inhibitors |
WO2023012669A2 (en) | 2021-08-03 | 2023-02-09 | Glaxosmithkline Intellectual Property Development Limited | Biopharmaceutical compositions and stable isotope labeling peptide mapping method |
WO2023027177A1 (en) | 2021-08-26 | 2023-03-02 | 協和キリン株式会社 | Bispecific antibody that binds to cd116 and cd131 |
WO2023039488A1 (en) | 2021-09-09 | 2023-03-16 | Iovance Biotherapeutics, Inc. | Processes for generating til products using pd-1 talen knockdown |
WO2023049862A1 (en) | 2021-09-24 | 2023-03-30 | Iovance Biotherapeutics, Inc. | Expansion processes and agents for tumor infiltrating lymphocytes |
WO2023056362A1 (en) | 2021-09-30 | 2023-04-06 | Seagen Inc. | B7-h4 antibody-drug conjugates for the treatment of cancer |
WO2023057893A1 (en) | 2021-10-05 | 2023-04-13 | Glaxosmithkline Intellectual Property Development Limited | Combination therapies for treating cancer |
EP4162950A1 (en) | 2021-10-08 | 2023-04-12 | Suzhou Abogen Biosciences Co., Ltd. | Nucleic acid vaccines for coronavirus |
WO2023064958A1 (en) | 2021-10-15 | 2023-04-20 | Compugen Ltd. | Combination therapy with anti-pvrig antibodies formulations, anti-tigit antibodies, and anti-pd-1 antibodies |
WO2023077015A2 (en) | 2021-10-27 | 2023-05-04 | Iovance Biotherapeutics, Inc. | Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy |
WO2023073615A1 (en) | 2021-10-29 | 2023-05-04 | Janssen Biotech, Inc. | Methods of treating crohn's disease with anti-il23 specific antibody |
WO2023079086A1 (en) | 2021-11-05 | 2023-05-11 | Astrazeneca Uk Limited | Composition for treatment and prevention of covid-19 |
WO2023086803A1 (en) | 2021-11-10 | 2023-05-19 | Iovance Biotherapeutics, Inc. | Methods of expansion treatment utilizing cd8 tumor infiltrating lymphocytes |
WO2023084488A1 (en) | 2021-11-15 | 2023-05-19 | Janssen Biotech, Inc. | Methods of treating crohn's disease with anti-il23 specific antibody |
WO2023091968A1 (en) | 2021-11-17 | 2023-05-25 | Disc Medicine, Inc. | Methods for treating anemia of kidney disease |
WO2023095000A1 (en) | 2021-11-23 | 2023-06-01 | Janssen Biotech, Inc. | Method of treating ulcerative colitis with anti-il23 specific antibody |
WO2023094507A1 (en) | 2021-11-24 | 2023-06-01 | Formycon Ag | Improved ace2 fusion proteins |
WO2023094571A1 (en) | 2021-11-25 | 2023-06-01 | Formycon Ag | Stabilization of ace2 fusion proteins |
WO2023114951A1 (en) | 2021-12-17 | 2023-06-22 | Viiv Healthcare Company | Combination therapies for hiv infections and uses thereof |
WO2023139107A1 (en) | 2022-01-18 | 2023-07-27 | argenx BV | Galectin-10 antibodies |
WO2023147399A1 (en) | 2022-01-27 | 2023-08-03 | The Rockefeller University | Broadly neutralizing anti-sars-cov-2 antibodies targeting the n-terminal domain of the spike protein and methods of use thereof |
WO2023147488A1 (en) | 2022-01-28 | 2023-08-03 | Iovance Biotherapeutics, Inc. | Cytokine associated tumor infiltrating lymphocytes compositions and methods |
WO2023147486A1 (en) | 2022-01-28 | 2023-08-03 | Iovance Biotherapeutics, Inc. | Tumor infiltrating lymphocytes engineered to express payloads |
US12030927B2 (en) | 2022-02-18 | 2024-07-09 | Rq Biotechnology Limited | Antibodies capable of binding to the spike protein of coronavirus SARS-CoV-2 |
WO2023172883A1 (en) | 2022-03-07 | 2023-09-14 | Alpine Immune Sciences, Inc. | Immunomodulatory proteins of variant cd80 polypeptides, cell therapies thereof and related methods and uses |
WO2023170290A1 (en) | 2022-03-11 | 2023-09-14 | Janssen Pharmaceutica Nv | Multispecific antibodies and uses thereof |
WO2023170291A1 (en) | 2022-03-11 | 2023-09-14 | Janssen Pharmaceutica Nv | Multispecific antibodies and uses thereof |
WO2023170295A1 (en) | 2022-03-11 | 2023-09-14 | Janssen Pharmaceutica Nv | Multispecific antibodies and uses thereof |
WO2023178192A1 (en) | 2022-03-15 | 2023-09-21 | Compugen Ltd. | Il-18bp antagonist antibodies and their use in monotherapy and combination therapy in the treatment of cancer |
EP4245374A2 (en) | 2022-03-18 | 2023-09-20 | Compugen Ltd. | Pvrl2 and/or pvrig as biomarkers for treatment |
WO2023187707A1 (en) | 2022-03-30 | 2023-10-05 | Janssen Biotech, Inc. | Method of treating mild to moderate psoriasis with il-23 specific antibody |
WO2023187657A1 (en) | 2022-03-30 | 2023-10-05 | Novartis Ag | Methods of treating disorders using anti-natriuretic peptide receptor 1 (npr1) antibodies |
WO2023187407A1 (en) | 2022-04-01 | 2023-10-05 | Bradcode Limited | Human monoclonal antibodies binding to sars-cov-2 and methods of use thereof |
WO2023196877A1 (en) | 2022-04-06 | 2023-10-12 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
US11981921B2 (en) | 2022-04-15 | 2024-05-14 | Iovance Biotherapeutics, Inc. | TIL expansion processes using specific cytokine combinations and/or AKTi treatment |
WO2023201369A1 (en) | 2022-04-15 | 2023-10-19 | Iovance Biotherapeutics, Inc. | Til expansion processes using specific cytokine combinations and/or akti treatment |
WO2023212304A1 (en) | 2022-04-29 | 2023-11-02 | 23Andme, Inc. | Antigen binding proteins |
WO2023209177A1 (en) | 2022-04-29 | 2023-11-02 | Astrazeneca Uk Limited | Sars-cov-2 antibodies and methods of using the same |
WO2023220608A1 (en) | 2022-05-10 | 2023-11-16 | Iovance Biotherapeutics, Inc. | Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with an il-15r agonist |
WO2023223265A1 (en) | 2022-05-18 | 2023-11-23 | Janssen Biotech, Inc. | Method for evaluating and treating psoriatic arthritis with il23 antibody |
WO2023242362A1 (en) | 2022-06-15 | 2023-12-21 | argenx BV | Fcrn/antigen-binding molecules and methods of use |
WO2023242372A1 (en) | 2022-06-15 | 2023-12-21 | argenx BV | Fcrn/hsa binding molecules and methods of use |
WO2023242361A1 (en) | 2022-06-15 | 2023-12-21 | argenx BV | Fcrn binding molecules and methods of use |
WO2023245048A1 (en) | 2022-06-15 | 2023-12-21 | Bioverativ Usa Inc. | Anti-complement c1s antibody formulation |
WO2023250507A1 (en) | 2022-06-24 | 2023-12-28 | Bioverativ Usa Inc. | Methods for treating complement-mediated diseases |
WO2024011114A1 (en) | 2022-07-06 | 2024-01-11 | Iovance Biotherapeutics, Inc. | Devices and processes for automated production of tumor infiltrating lymphocytes |
WO2024020407A1 (en) | 2022-07-19 | 2024-01-25 | Staidson Biopharma Inc. | Antibodies specifically recognizing b- and t-lymphocyte attenuator (btla) and uses thereof |
WO2024020579A1 (en) | 2022-07-22 | 2024-01-25 | Bristol-Myers Squibb Company | Antibodies binding to human pad4 and uses thereof |
WO2024026386A1 (en) | 2022-07-27 | 2024-02-01 | Cephalon Llc | Anti-tl1a antibody formulations |
WO2024026395A1 (en) | 2022-07-27 | 2024-02-01 | Cephalon Llc | Anti-tl1a antibodies for the treatment of ulcerative colitis and crohn's disease |
WO2024026496A1 (en) | 2022-07-28 | 2024-02-01 | Compugen Ltd. | Combination therapy with anti-pvrig antibodies formulations and anti-pd-1 antibodies |
WO2024030758A1 (en) | 2022-08-01 | 2024-02-08 | Iovance Biotherapeutics, Inc. | Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies |
WO2024044675A1 (en) | 2022-08-25 | 2024-02-29 | Beigene, Ltd. | Methods of cancer treatment using anti-pd1 antibodies in combination with anti-tim3 antibodies |
WO2024042112A1 (en) | 2022-08-25 | 2024-02-29 | Glaxosmithkline Intellectual Property Development Limited | Antigen binding proteins and uses thereof |
WO2024050524A1 (en) | 2022-09-01 | 2024-03-07 | University Of Georgia Research Foundation, Inc. | Compositions and methods for directing apolipoprotein l1 to induce mammalian cell death |
WO2024052503A1 (en) | 2022-09-08 | 2024-03-14 | Institut National de la Santé et de la Recherche Médicale | Antibodies having specificity to ltbp2 and uses thereof |
WO2024062074A1 (en) | 2022-09-21 | 2024-03-28 | Sanofi Biotechnology | Humanized anti-il-1r3 antibody and methods of use |
WO2024061930A1 (en) | 2022-09-22 | 2024-03-28 | Institut National de la Santé et de la Recherche Médicale | New method to treat and diagnose peripheral t-cell lymphoma (ptcl) |
WO2024077018A2 (en) | 2022-10-04 | 2024-04-11 | Alpine Immune Sciences, Inc. | Methods and uses of taci-fc fusion immunomodulatory protein |
WO2024089609A1 (en) | 2022-10-25 | 2024-05-02 | Ablynx N.V. | Glycoengineered fc variant polypeptides with enhanced effector function |
WO2024098027A1 (en) | 2022-11-04 | 2024-05-10 | Iovance Biotherapeutics, Inc. | Methods for tumor infiltrating lymphocyte (til) expansion related to cd39/cd103 selection |
WO2024098024A1 (en) | 2022-11-04 | 2024-05-10 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof |
WO2024112571A2 (en) | 2022-11-21 | 2024-05-30 | Iovance Biotherapeutics, Inc. | Two-dimensional processes for the expansion of tumor infiltrating lymphocytes and therapies therefrom |
WO2024112711A2 (en) | 2022-11-21 | 2024-05-30 | Iovance Biotherapeutics, Inc. | Methods for assessing proliferation potency of gene-edited t cells |
WO2024110898A1 (en) | 2022-11-22 | 2024-05-30 | Janssen Biotech, Inc. | Method of treating ulcerative colitis with anti-il23 specific antibody |
WO2024110905A1 (en) | 2022-11-24 | 2024-05-30 | Beigene, Ltd. | Anti-cea antibody drug conjugates and methods of use |
WO2024121126A1 (en) | 2022-12-05 | 2024-06-13 | Institut Regional Du Cancer De Montpellier | Anti-slc1a4 monoclonal antibodies and uses thereof |
EP4382120A1 (en) | 2022-12-05 | 2024-06-12 | Institut Regional du Cancer de Montpellier | Anti-slc1a4 monoclonal antibodies and uses thereof |
EP4386084A1 (en) | 2022-12-14 | 2024-06-19 | Formycon AG | Improved ace2 fusion proteins |
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